Menaechmi, a Latin-language play, is often considered Plautus' greatest play. The title is sometimes translated as The Brothers Menaechmus or The Two Menaechmuses.

Menaechmi is a comedy about mistaken identity, involving a set of twins, Menaechmus of Epidamnus and Menaechmus of Syracuse. It incorporates various Roman stock characters including the parasite, the comic courtesan, the comic slave, the domineering wife, the doddering father-in-law and the quack doctor. As with most of Plautus' plays, much of the dialogue was sung.

The play is set in a street in Epidamnus, a city on the coast of what is now Albania. Facing the audience are two houses, that of Menaechmus I and that of Erotium, the prostitute he is courting.

Prologue: Moschus has twin sons, Menaechmus and Sosicles. Moschus decides to take only one of the twins, Menaechmus, with him on a business trip, while the twins are still young. During the trip, Menaechmus is abducted and adopted by a businessman who lives in Epidamnus, separating the twins. Their father dies of sorrow and their grandfather changes Sosicles' name to Menaechmus (i.e., Menaechmus of Syracuse). When the twins are grown to manhood, Menaechmus of Syracuse sets out in search of his brother. He arrives in Epidamnus, unaware that his twin brother is there also.

Act 1: Here, the brother is first shown to be, with good cause, the despair of his jealous wife. He is seen leaving his house, berating his spouse as a shrew and a harpy, promising that she shall have good cause for her jealousy. He confides to Peniculus, a professional parasite, that he has stolen his wife's mantle and is going to give it to Erotium, a prostitute who lives next door.

The two go to Erotium's door, and the husband presents the mantle with many blandishments. He suggests that a fitting return would include a dinner for himself and Peniculus. Erotium agrees, and the two men go to the Forum for preliminary drinks while the meal is being prepared.

Act 2: Meanwhile, the twin from Syracuse has arrived with Messenio, his slave. The latter warns him of the depravity of Epidamnus, urging an end to the search for his missing brother since their money is nearly gone. His master gives his purse for safekeeping to the slave who continues his warning against the cunning people of Epidamnus "who think nothing of accosting a stranger" and bilking him of his money, when Erotium steps out of her house and endearingly accosts the Syracuse Menaechmus, thinking him to be his brother.

She asks why he hesitates to enter when dinner is ready, and the confused twin asks her, quite formally, what business he has with her. Why, the business of Venus, Erotium replies coyly. Messenio whispers to his master that the lady undoubtedly is a schemer for his money, and asks her if she knows his master. He is Menaechmus, of course, replies Erotium. This amazes the twin, but Messenio explains that spies of the city's thieves probably have learned his name.