Hypogonadism is a common condition, especially among older men, but often goes undiagnosed and untreated. It can be associated with a number of signs and symptoms that affect health and quality of life, including feelings of low energy and fatigue; decreased sex drive and performance; decreased muscle mass and strength; decreased bone mineral density; and increased body fat, particularly abdominal fat, a putative risk factor for metabolic syndrome and type 2 diabetes mellitus. The evidence supporting testosterone replacement therapy (TRT) in improving these and related conditions is strong and consistent for body composition and sexual function; moderately consistent for bone mineral density; inconsistent for insulin sensitivity, glycemic control, and lipid profiles; and weak and inconsistent for mood and cognitive function. The concern of some physicians about the potential for TRT to stimulate prostate cancer is not supported by decades of data accumulated to date, though studies of longer duration (eg, 10 years or more) would be even more convincing. Other research needs are discussed. As the front line of health care delivery, primary care physicians need to be vigilant in diagnosing and treating symptomatic hypogonadism. Based on current guidelines, we recommend assessing testosterone levels when an adult man exhibits signs of hypogonadism, and as part of normal medical screening in men starting at age 40 to 50 years, to establish a baseline. A physician should discuss the possibility of TRT with symptomatic patients who have a serum total testosterone level < 300 ng/dL. If TRT is initiated, a patient's response and adverse events should be assessed every 3 to 6 months, and therapy adjusted accordingly.