“Retinoid” refers to the naturally occurring compounds with vitamin A activity and to synthetic analogues of retinol. Retinoids are key regulators of differentiation, proliferation, and inflammation. Their successful use in the treatment of various skin diseases and neoplasias has revolutionized the practice of dermatology as well as oncology. This article focuses on the retinoid receptors to elucidate our understanding of their complex biologic activity that is reflected in their therapeutic clinical effects as well as in their adverse reactions.