If a cocktail is an ensemble cast, consider bitters (or amari in Italian) that outlier who always shows up at the right moment to deliver the perfect quip. Without bitters, the classic Manhattan cocktail would be “My Best Friend’s Wedding” sans Rupert Everett — all saccharine, no wit.

“Bitters are like a liquid spice rack,” says Brad Thomas Parsons, author of “Bitters: A Spirited History of a Classic Cure-all” ($25, Ten Speed Press). “In a cocktail, they help unify disparate ingredients and transform them into something much greater than the sum of its parts.”

During Prohibition, bitters emerged as a so-called cure-all. Though the stuff — a strong solution of herbs, spices, roots and a base spirit — can pack a 90-proof punch, stores labeled the bottles “non-potable,” allowing people to buy it legally. That loophole endures still in some liquor-free zones such as Virginia grocery stores, says Scott Clime, beverage director of DC Coast (1401 K St. NW; 202-216-5988) and its family of restaurants.

These days, the infused spirit remains a tonic — for bored drinkers.

“Bitters are being rediscovered,” says David Bueno, beverage director of Quill, the VIP-heavy bar inside the Jefferson Hotel, where the fall cocktail menu features the On the Road, a rye whiskey elixir with a bitter edge thanks to beet syrup, rhubarb bitters and Aperol (like Campari, but less potent). “To have a good bitters collection is a synonym of having a good bar.” That’s in part because the biggest fans of bitters are the discerning folks tending and stocking that bar.

“Bitters are in the core definition of a cocktail; the first written description of the word classified it as ‘spirits of any kind, sugar, water and bitters,’ ” Parsons says.

That’s where things start to get fun — and complicated. D.C.’s top bars tout dozens of varieties and an array of brands. As in most areas of the kitchen, home bartenders can start by stocking the basics; later comes boutique varieties, from barrel-aged to such exotic flavors as black mission fig. Just don’t expect to taste a huge difference between varieties, especially as a novice taster. Here it’s all in the nose — and in the pairings.

“Angostura is a must-have: Look for the bright yellow cap and oversize label next to the maraschino cherries and cocktail onions,” Parsons says. Whiskey lovers should gravitate to orange or rye-based bitters, Clime says, while Peychaud’s bitters are the secret to the old-school Sazerac. Try celery and rhubarb bitters with gin; Mexican molé bitters hold their own against tequila. Just remember: Shyness here is a virtue; start with just a dash or two.

“Bitters are like salt,” Bueno says. “You want to put just enough to make it good. Too much, and it’s undrinkable.”

Once you’ve gotten your bitter tongue in check, the next step in bitters sophistication is to explore the Italian amaro family of infused spirits — the kind you drink rather than dash, from caramely Amaro Averna to Cynar, an artichoke-based liqueur. Even better are the cool cocktails that star amari, from the Campari-heavy Negroni to the Argentine party drink the “Fernando,” i.e. sharp Fernet Branca (see sidebar for more information) sweetened with Coca-Cola.

At Italian power spot Fiola (601 Pennsylvania Ave. NW; 202-628-2888), mixologist Jeff Faile pays tribute to the Negroni with seven types, from a twist on the classic recipe that swaps Campari for Gran Classico to the bright Bianco, with gin, floral-forward dolin blanc and Cocchi Americano that he calls the perfect introduction to the Negroni. “The Negroni is simple to make, but there’s so much flavor in just three ingredients,” Faile says. (His pick for the best all-around Negroni vermouth: Dolin Rouge.)

Alexandra Bookless, head bartender of the Passenger (1021 7th St. NW; 202-393-0220), is bitter-tongued by choice and trade.

Alexandra Bookless, head bartender at the Passenger, mixes numerous cocktails starring amari, aka Italian bitters. She says customers enjoy their complex flavors.

“I like the classic Hanky Panky cocktail, which has gin, sweet vermouth and Fernet,” she says.

She also makes a cocktail called the Letizia, with Averna, fresh grapefruit juice and tonic over crushed ice, and her favorite amari include Amaro Nonino, Averna and Fernet Branca — so much so that the spirit becoming synonymous with the San Francisco drinking scene has its own tap at the Passenger.

Novices might start out drinking amari with tonic or soda water and a slice of grapefruit or orange.

“You can also try substituting amari into one of your favorite drinks in place of Campari or vermouth, or you can drink it straight like I do,” Bookless says. “The spirits are complicated and balanced with tons of herbal notes — and they come pre-mixed. And amari have a refreshing effect on my palate, which is nice when you spend the day cramming all sorts of tastes into your palate.”

Indeed, there’s a reason amari lives on the menu as pre- or post-dinner tipples.

“Bitterness keeps the appetite — and thirst — awake,” Bueno says. “It’s the bitter flavor that keeps you wanting more.”

Not-So-Sweet Stuff

In 1960, actor Tony Randall (of TV’s “The Odd Couple”) famously took a sip from his onstage drink — and immediately assumed his cocktail had been laced with poison. Nope. Just a little Fernet Branca, a sharp and syrupy aromatic known for its bitter iodine edge.

“Bitterness is a natural indicator of toxicity, which is harmful to our bodies,” says Kendall Eskine, a professor of psychology at the City University of New York, who recently published a study that found that gustatory disgust can influence moral judgment (there’s a reason Champagne calls for a party, while downing a bottle of bitters would call for a psychiatrist). “That instinct is why young children tend not to like dark-green, leafy vegetables, and why pregnant women tend to experience a heightened sense of taste and smell — particularly to bitterness — in order to protect their offspring from potential threats.”

Consider it the fight-or-flight response. “If we don’t know a food or drink is bitter and we are surprised, we generally don’t like it,” says Danielle Reed, a geneticist at Philadelphia’s Monell Chemical Senses Center. “When we know that a food or drink is bitter, and especially if we have learned to pair that food with a drug such as caffeine in coffee, we like it better.”