Tazarotene belongs to a novel, nonisomerizable class of retinoic acid receptor (RAR)-specific retinoids, the acetylenic retinoids, and is the first topical retinoid developed for the treatment of psoriasis. Tazarotene targets the keratinocyte and modulates the major causes of psoriasis. Tazarotene is rapidly metabolized by esterase to the active free acid tazarotenic acid, which is rapidly eliminated in animal species. Tazarotene selectively transactivates RARβ and RARγ subtypes and is inactive at retinoid X receptors (RXRs). This receptor selectivity could contribute to an optimized therapeutic index. Tazarotene has low systemic absorption after topical administration. In preclinical toxicity studies, high topical doses produced reversible topical irritation, and lower doses were well tolerated. Topical doses were neither teratogenic nor carcinogenic and were not sensitizing, phototoxic, or photosensitizing. The topical delivery of tazarotene and limited systemic exposure apparently result in a very low potential for systemic effects. (J Am Acad Dermatol 1997; 37: S12–S17.)