Black Books is a second-hand bookshop in London run by an Irishman named Bernard Black. He is probably the planet's worst-suited person to run such an establishment: he makes no effort to sell, closes at strange hours on a whim, is in a perpetual alcoholic stupor, abhors his customers (sometimes physically abusing them) and is often comatose at his desk. Help comes in the lumpy shape of Manny Bianco, a hairy, bumbling individual who (almost by osmosis) becomes Bernard's assistant. Manny is not exactly great at the job either but he is a million times better than Bernard. Next door is Fran, an anxious, frustrated woman who runs a sort of new-age shop selling the most unlikely bits of arty junk. Fran is friends with Bernard and, through him, with Manny; together the trio become embroiled in escapades that are sometimes extreme or violent or fantastically ludicrous, and always bizarre.
Fran buys a piano and starts taking lessons, discovering she has no talent whatsoever - meanwhile Bernard falls in love and tries desperately to impress her. Between them, they con Manny into throwing away a hard-earned break to help them out.
As the temperature creeps slowly towards 88 degrees, Manny desperately seeks out new ways to stay cool, lest he trigger his "Dave syndrome." Meanwhile an unsympathetic Bernard falls hopelessly in love with Fran's new neighbour, who is unknowingly taking over Fran's apartment.
Bernard and Manny need to teach a psychotic ex-con to read in three days after agreeing to host his reading and book-signing in the shop. Fran gets a new job and all seems to be going well until some miscommunication when Manny calls in a favour...
When Manny is drawn into a competing bookstore by its customer-friendly atmosphere, he convinces Bernard the shop needs an overhaul. Fran makes use of the shop's improved facilities to track down her relatives, but is not entirely happy with what she finds.
Fran starts spending time with a new-age friend to try and wind down while Bernard and Manny are having another fight. Bernard believes Manny is a psychopath and sends him to a therapist, where he unlocks a confidence he never knew he had.
Bernard and Manny can't hear themselves argue because the shop next door is undergoing some round-the-clock construction. The noise drives Bernard, Manny and Fran up the wall. So Fran suggests a holiday. Bernard and Manny find baggage in her luggage. There's nothing in the crisp packet and Manny's pants aren't that easy to fold. Will the customer crack the system? What happens on the riverboat? Just how many monkeys are missing in Canada?