Acne is a disease of the pilosebaceous unit, involving abnormalities in sebum production, follicular epithelial desquamation, bacterial proliferation, and inflammation. The major classes of therapeutic agents are topical and systemic retinoids, antimicrobial agents, and systemic hormonal drugs. Combination therapy with a topical retinoid and an antibiotic can normalize follicular epithelial desquamation and reduce bacterial proliferation. The new retinoids (eg, adapalene) have an additional antiinflammatory action along with their effect on the preclinical microcomedo and, coadministered with a topical or an oral antibiotic, are a rational initial therapy for all but the most severe forms of acne. Retinoids can also be used alone for long-term maintenance to prevent the reemergence of comedones and inflammatory acne lesions and to spare the use of antibiotics, thus helping to reduce the risk of bacterial resistance.