This chapter aims to cover discussion on macrolides and chemotherapy of sexually transmitted diseases. Erythromycin, roxithromycin, clarithromycin, azithromycin, oleandomycin, spiramycin are the macrolide antibiotics. They are called ‘macrolide’ because of their large (macro) chemical structure. Erythromycin is available as erythromycin estolate and erythromycin stearate. Erythromycin estolate cause less GIT upset, is better absorbed however, it causes hepatotoxicity with cholestatic jaundice. Roxithromycin, clarithromycin, azithromycin, ketolides, chemotherapy of sexually transmitted diseases, and chemoprophylaxis of sexually transmitted diseases are the topics which are discussed in this chapter.