Testosterone deficiency, or male hypogonadism, is a clinical syndrome that can be defined as persistently low serum testosterone levels in the setting of symptoms consistent with testosterone deficiency. Studies suggest that testosterone replacement therapy may improve sexual function, depressive symptoms, bone density, and lean body mass. Evidence is conflicting regarding its effect on cardiovascular events and mortality. Although prior studies suggested that testosterone replacement therapy increased the risk of cardiovascular disease, a large, randomized trial showed that it does not increase the risk of myocardial infarction or stroke, even in patients at high risk. After a detailed discussion of the potential benefits and risks through shared decision-making, testosterone replacement therapy should be considered for men with testosterone deficiency to correct selected symptoms and induce and maintain secondary sex characteristics. Treatment method should take into consideration patient preference, pharmacokinetics, potential for medication interactions, formulation-specific adverse effects, treatment burden, and cost. Clinicians should monitor men receiving testosterone replacement therapy for symptom improvement, potential adverse effects, and adherence. Serum testosterone, hematocrit, and prostate-specific antigen levels should be measured at baseline and at least annually in men 40 years or older receiving testosterone replacement therapy. (Am Fam Physician. 2024;109(6):543-549. Copyright © 2024 American Academy of Family Physicians.)