Annona muricata L. is a plant belonging to the Annonaceae family and is highly appreciated for its bioactive compound content; between them are acetogenins. Acetogenins are molecules with aliphatic chains and a lactonic group, and they have been isolated from various parts of the tree (leaves, stem, and root) or fruit (peel, pulp, columella, and seeds). Also, they present different biological activities such as insecticidal, antiviral, and antitumoral. However, has it been demonstrated that acetogenins are antimicrobial. This chapter aims to show the scientific evidence of the antimicrobial effect of crude extracts or acetogenins isolated from Annona muricata on Gram-positive and Gram-negative bacteria and some yeasts.