Acne vulgaris is a common condition that can be socially isolating and physically scarring. It affects almost everyone at some point in life. As an inflammatory condition worsened by colonization with Propionibacterium acnes, it often requires systemic antibiotics for adequate treatment. Many different antimicrobials have been used over the past 5 decades to treat acne. First-line antibiotic therapy has included the tetracyclines as well as the macrolides, most commonly erythromycin. Because of increasing bacterial resistance to erythromycin, many dermatologists are now using azithromycin, a different macrolide, to combat acne. This article reviews the literature describing the use of azithromycin against acne.