Bacterial resistance became a true clinical concern for dermatologists in the 1980s, when the first reports emerged of the resistance of Propionibacterium acnes to oral antibiotics. Subsequent studies have documented acne treatment failure associated with resistance to topical antibiotics. Beyond dermatology practice, antibiotic resistance has now become recognized as a worldwide health concern. In contrast to antibiotics commonly used in the treatment of acne, benzoyl peroxide (BP)'s mechanism of action is different. Benzoyl peroxide is a bactericidal agent. Combining BP with a topical antibiotic in a stable formulation has been proven in clinical trials to reduce total P acnes count by 99.7% after 1 week of therapy, eliminating both susceptible and resistant strains of P acnes. However, we have recently noticed BP's benefits as monotherapy in the treatment of acne. Benzoyl peroxide works rapidly on P acnes without causing antibiotic resistance. Hence, we may have to reconsider the role of topical antibiotics such as clindamycin in the treatment paradigm of acne vulgaris.