Systemic dapsone therapy has historically been used to treat leprosy, inflammatory dermatoses, and severe cases of acne vulgaris. This article reviews the pharmacokinetics, short and long-term safety, drug-drug interactions, gender, and age effects of topical dapsone 5% and 7.5% gel formulations. In 20 human studies and 7 case reports, 39 of 6,384 total patients (<1%) experienced adverse effects that were considered more than mild or resulted in discontinuation of topical dapsone. The literature supports topical dapsone 5% and 7.5% gels as safe and effective medications for the treatment of dermatologic disease.