The play is set in Messina and revolves around two romantic pairings that emerge when a group of soldiers arrive in the town. The first, between Claudio and Hero, is nearly scuppered by the accusations of the villain, Don John. The second, between Claudio's friend Benedick and Hero's cousin Beatrice, takes centre stage as the play continues, with both characters' wit and banter providing much of the humour.

Through "noting" (sounding like "nothing" and meaning gossip, rumour, overhearing),[2][3] Benedick and Beatrice are tricked into confessing their love for each other, and Claudio is tricked into believing that Hero is not a maiden (virgin). The title's play on words references the secrets and trickery that form the backbone of the play's comedy, intrigue, and action.