This week, we got a sense of who might determine the fate of President Biden’s agenda in the months to come. Both Sens. Joe Manchin III (D-W.Va.) and Kyrsten Sinema (D-Ariz.) said they would not support eliminating the filibuster and couldn’t be convinced otherwise, undercutting efforts by more liberal elements of the party to eliminate the 60-vote threshold for passing most legislation.

The two senators’ presence as a potential impediment to Biden’s agenda is no surprise. They have been among the most moderate Democratic senators since joining the chamber. But given the setup of the 50-50 Senate — in which Democrats would need 10 GOP votes to clear filibusters and few or no defections to pass other legislation — plenty of lawmakers could be pivotal.

Below is a look at who could figure prominently in that in the months and years ahead.

Sen. Joe Manchin III (D-W.V.a.)

Nobody in the Democratic caucus will feel the pull of the Biden opposition as much as Manchin. West Virginia was the second-Trumpiest state in both the 2016 and the 2020 elections, behind only Wyoming in both cases. Manchin has more of a brand in his state than almost any other senator, having been a former governor, but even that has limits — especially in a Democratic administration.

The existence of the filibuster means Manchin won’t be in the position of being the decisive 50th vote on much legislation, with the notable exceptions of judicial nominees and bills considered under reconciliation, the apparent destiny of Biden’s coronavirus stimulus. But even when the threshold is 60 votes, to the extent Democrats can’t get Manchin onboard with Biden’s agenda, it will make it much easier for Republicans to balk.

Sen. Kyrsten Sinema (D-Ariz.)

The senator from Arizona is something of a political enigma. Early in her career, she aligned with the Green Party, but in both the House and Senate she has represented competitive areas — including now representing one of the most competitive states in the country, which had gone for only one Democrat since 1948 before Biden’s win.

And she has crafted a moderate path throughout — more so than even her state might dictate. FiveThirtyEight’s vote rankings put her behind only Manchin among current Democratic senators when it comes to how often she voted with President Donald Trump — slightly more than 50 percent of the time. And she ranked No. 1 among Democrats when it came to how pro-Trump her voting record was relative to her home state. (Every other Democratic senator who voted more pro-Trump than expected came from a heavily blue state.)

Sinema, unlike some senators on this list, isn’t up for reelection until 2024, but she has shown a penchant for lawmaking from the middle even removed from such considerations.

Retiring GOP senators

Biden, as noted above, will need GOP votes to pass the vast majority of his agenda. And high on the list of potential Senate crossovers will surely be the usual suspects — with blue-state Republican Susan Collins (R-Maine) and Alaska’s Lisa Murkowski being at the top of that list, given their frequent hesitations about supporting Trump’s agenda. (Murkowski voted against proceeding on Supreme Court nominee Amy Coney Barrett’s nomination before the election, although she eventually supported it once the vote happened. She also hesitated on Brett M. Kavanaugh’s nomination and has criticized Trump during both impeachment processes.)

But when it comes to reaching 60 votes rather than 50, their support will mostly be necessary rather than sufficient. You need to look elsewhere in the caucus to reach that threshold. And high on that list are a trio of retiring senators — North Carolina’s Richard Burr, Pennsylvania’s Patrick J. Toomey and Ohio’s Rob Portman, who announced his exit Tuesday — along with other potential retirees who often have more latitude to take tough votes. Another who could join that list is Sen. Charles E. Grassley (R-Iowa). Like the others, he comes from a competitive state, but he hasn’t committed to seeking reelection in 2022, when he would be 89 years old.

Even if more middle-of-the-road GOP senators are onboard, these votes won’t be sufficient to get to 60. But they will be paramount when it comes to whether votes will be close.

House Democrats

While so much of the focus has been on the Senate amid the filibuster debate, we often lose sight of how much of an impediment House Democrats could be. The party has about a 10-seat majority, depending on how things shake out in some outstanding races, meaning they can lose only around five votes.

Among those who could face tough votes in Trump-supporting districts: Reps. Jared Golden (D-Maine), Ron Kind (D-Wis.), Andy Kim (D-N.J.), Elissa Slotkin (D-Mich.) and Cheri Bustos (D-Ill.). There’s no real Blue Dog presence in the modern Democratic Party like there used to be, and these members generally come from close districts, but they could face tough votes, and Biden need not lose many of them to see a bill killed.

Of course, in cases in which the Senate threshold is 60 votes, losing these votes means it almost definitely couldn’t pass the Senate anyway.

Sen. Mitt Romney (R-Utah)

The senator from Utah has often been falsely branded as a moderate; his objections to Trump and Trumpism almost always pertained to Trump’s character and conduct rather than the conservatism of legislation. But he’s still a vote worth watching, as someone — like Manchin — with some leverage based upon his in-state brand and his willingness to buck his party.

Nobody should expect Romney to become Biden’s best friend, but he has set himself up as a vote worth watching as a potential dealmaker. And if he’s onboard in such a red, anti-Biden state, it could give others cover.

Sen. Jon Tester (D-Mont.)

Apart from Manchin, only two current Democratic senators come from states that went red in the 2020 election. One of them is Sen. Sherrod Brown (D-Ohio), whose liberal bona fides are well-established. The other is more of a wild card: Tester.

Tester’s voting record is on the complete opposite end of the spectrum from Sinema’s — that is, more than any other senator, he voted more often against Trump than his constituency would suggest. That could indicate he might be a reliable vote for Biden’s agenda, given how much he opposed Trump’s. But being in the majority and supporting things — rather than opposing them — can be a different exercise. And Tester has less latitude to craft a liberal record than someone like Brown.

Like Sinema, he is not up until 2024, and that matters, but he’s still completely worth watching, given the state he comes from.

Sens. Mark Kelly (D-Ariz.) and Raphael G. Warnock (D-Ga.)

Both of the new Democratic senators have the pleasure of running again in 2022 after winning special elections, and both come from extremely close states. Neither really ran as a moderate, though, and Warnock in particular doesn’t seem like he’ll be high on the list of tough votes for Biden. But if things get difficult and the 50-vote threshold is the key one for big votes, they could matter.

Sens. Maggie Hassan (D-N.H.) and Catherine Cortez Masto (D-Nev.)

Beyond those two, the New Hampshire and Nevada senators come from about the only two states that seem potentially competitive in 2022, although both states have trended blue in recent years.