Testosterone replacement therapy is approved for the treatment of hypogonadism in men. However, the long-term cardiovascular safety of testosterone replacement therapy in middle-aged and older men with hypogonadism has been a subject of much controversy. The TRAVERSE trial, a large, randomized placebo-controlled cardiovascular safety trial of testosterone replacement therapy in middle-aged and older men with hypogonadism and either preexisting cardiovascular disease or increased risk of cardiovascular disease demonstrated that testosterone treatment was noninferior to placebo with respect to the incidence of major adverse cardiovascular events. Testosterone treatment was associated with higher incidence of venous thromboembolism and atrial fibrillation than placebo. The decision to treat middle-aged and older men with hypogonadism should be guided by consideration of the severity of testosterone deficiency, the burden of symptoms, and an individualized assessment of potential benefits and risks of testosterone replacement therapy.