Vitamin A, all-trans-retinoic acid, and its metabolites play an important gene-regulatory and epigenetic role in the development and function of endocrine glands. Therapeutic doses of retinoids evoke aberrant gene-regulatory and epigenetic reactions that often adversely affect endocrine and metabolic systems. Synthetic retinoids have an endocrine effect on the thyroid axis. All retinoids in clinical use, i.e., isotretinoin, alitretinoin, acitretin, and bexarotene, may negatively affect lipid and lipoprotein metabolism, primarily increasing the risk of hypertriglyceridemia, especially in individuals predisposed for hypertriglyceridemia. Patients using retinoids should be consulted for possible elevation in triglycerides and cholesterol levels, and treatment strategies should be established if hyperlipidemia develops. Retinoids have important roles in the development and function of the hormonal system and are critical regulators of gene expression. Synthetic retinoids affect epidermal barrier homeostasis. Side effects of systemic retinoids on the endocrine system are substantial and require intervention to control such retinoid-induced adverse effects as bexarotene-induced central hypothyroidism and retinoid-induced hyperlipidemia.