Acne vulgaris is a highly prevalent, multifactorial disease process affecting the pilosebaceous units of the dermis. The effects of acne are profound both physically and psychosocially across all age groups and ethnicities; therefore, prompt recognition and appropriate treatment are critical. Pharmacotherapeutic approaches range from simple monotherapy to multimodal treatments with a variety of topical and systemic agents. Optimal patient outcomes in acne management, however, are based both on treatment efficacy as well as overall patient satisfaction. In an effort to comprehensively address these key clinical considerations in acne management, we examine the diverse nature of acne patients, the factors in optimizing treatment outcomes, and the clinical impact of current medications, particularly topical combination therapy.