2021 is the 50th anniversary of the FDA approval of minocycline (MCN). While many other antibiotics have become obsolete during this time, MCN continues to be quite useful. In dermatology, MCN is used prominently in acne vulgaris, and is also employed in many other dermatological conditions because of its molecular and pharmacological properties. In this article, we review the history of minocycline, and outline the evolution of the drug since its inception. Based on its existing longstanding utility and continued innovations in formulation and delivery systems, we postulate that it will continue to have a prominent position in the dermatologist’s armamentarium. J Drugs Dermatol. 2021;20(10):1031-1036. doi:10.36849/JDD.6370.