Retinoids comprise a family of compounds with structures and mechanisms of action that resemble those of vitamin A (retinol), an essential nutrient which plays a role in cell growth and differentiation. The retinoids, which interact with nuclear receptors and affect gene transcription, have enormous therapeutic potential, particularly if they are receptor- and function-selective. Tretinoin was the first topical retinoid employed for the treatment of acne. In recent years, other topical retinoids for the treatment of acne have been designed from a disease-specific approach, with enhanced receptor and function selectivity, which translates to improved therapeutic effects and more favorable tolerability. The properties that differentiate the topical retinoids tretinoin, adapalene, and tazarotene have permitted clinicians to tailor acne treatment regimens for maximum therapeutic outcomes. Tretinoin (all-trans-retinoic acid), considered a first-generation retinoid, acts by altering the milieu of the microcomedo and influences desquamation of abnormal epithelium. Two receptor-selective synthetic retinoids, adapalene and tazarotene, may be classified as third-generation retinoids. Adapalene, a derivative of naphthoic acid, has comedolytic, antiproliferative, and anti-inflammatory properties. Tazarotene is a prodrug metabolized to tazarotenic acid that modulates cellular differentiation, desquamation, and inflammation.