Many innovations in acne therapy have evolved since the discovery in 1949 that vitamin A derivatives affected epidermal proliferation. Approval of topical tretinoin solution in 1971 was followed by modifications in the formulation to improve tolerability and provide flexibility in dosing. Identification of retinoid receptors led to research that resulted in 2 receptor-selective synthetic retinoids: adapalene and tazarotene. Today, topical retinoids are one of the cornerstones of acne therapy and are recommended as first-line therapy for all but the most severe forms of acne. They are used as monotherapy in mild comedonal acne; for inflammatory acne, topical retinoids are used in combination with benzoyl peroxide (BPO) and antibiotics (topical or oral) and/or hormonal therapy for females. Because of the high prevalence of antibiotic-resistant strains of Propionibacterium acnes, topical antibiotics should no longer be used as monotherapy. Topical retinoid monotherapy is recommended for maintenance because it prevents formation of microcomedones, the precursor lesions in acne. Combination topical retinoid/antimicrobial therapy has become the current recommended standard of care for the management of patients with acne. Combination therapy can target multiple pathogenic factors: abnormal follicular keratinization, P acnes proliferation, inflammation, and increased sebum production. A number of fixed-combination products are available. These products are effective, generally well-tolerated, and more convenient for patients than multiple individual agents. By reducing the number of medications and applications, fixed-combination products have the potential to improve patient adherence, thereby improving treatment outcomes.