INTRODUCTION: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a rare genetic condition characterized by cortisol deficiency and excess adrenal androgens. CAH treatment is a lifelong balancing act between the need to reduce excess androgens, typically with supraphysiologic glucocorticoid (GC) doses, and concerns about potentially serious GC-related adverse events. Tradeoffs between the consequences of excess androgens versus GCs must be constantly reassessed throughout each patient's lifetime, based on current clinical needs and treatment goals. Adding to this burden are limited treatment options and the need for new CAH medications. AREAS COVERED: This narrative review describes the current challenges of CAH treatment, the potential of new non-GC therapies to reduce excess androgens and thereby allow for lower GC doses, and the potential implications of decreasing GC doses to a more physiologic range (i.e. sufficient to replace missing cortisol, but without the need to reduce androgens). EXPERT OPINION: Even with non-GC therapies, patients' needs will continue to shift throughout their lifetimes. Treatment will therefore always require joint decision-making between physicians and patients. However, over the lifetimes of patients with CAH, any reduction in GC daily dose may have a large cumulative impact in decreasing the GC-related burden of this disease.