SUMMARY Testosterone is the primary androgenic hormone and is responsible for normal growth and development of male sex organs and maintenance of secondary sex characteristics. Pre-pubertal hypogonadism is generally characterized by infantile genitalia and lack of virilization, while the development of hypogonadism after puberty frequently results in complaints such as diminished libido, erectile dysfunction, infertility, gynecomastia, impaired masculinization, changes in body composition, reductions in body and facial hair, and osteoporosis. Hypogonadal men also report levels of anger, confusion, depression, and fatigue that are significantly higher than those reported in eugonadal men. Evaluation of potential candidates for testosterone replacement therapy should include a complete medical history and hormonal screening. Total serum testosterone should be measured in the morning. When the serum testosterone level is low and LH is elevated, testosterone replacement therapy is warranted. Patients with low serum LH and testosterone levels need an imaging study of their pituitary and may need endocrinologic consultation. Testosterone replacement should in theory approximate natural, endogenous production of the hormone. The clinical rationale for treatment of testosterone deficiency may include: stabilizing or increasing bone density; enhancing body composition by increasing muscle strength and reducing adipose tissue; improving energy and mood; and maintaining or restoring secondary sexual characteristics, libido, and erectile function. Several different types of testosterone replacement are currently marketed, including tablets, injectables, and transdermal systems. Oral testosterone is associated with elevations in liver function tests and abnormalities at liver scan and biopsy. While injectable testosterone is considered safe, fluctuations in testosterone levels may yield variations in libido, sexual function, energy, and mood, and patients may be inconvenienced by the need for frequent testosterone injections. Transdermal systems offer a convenient, though more costly, means of testosterone replacement and have demonstrated safety and efficacy in a number of clinical trials. The physician prescribing testosterone replacement should evaluate any changes in the clinical symptoms and signs of testosterone deficiency and should assess the patient by performing a DRE and checking serum testosterone levels, PSA, and hematocrit at baseline and at prescribed intervals during treatment. Although testosterone replacement is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate, in general, therapy appears to be safe for the vast majority of hypogonadal men. There is no apparent association between testosterone replacement therapy and the development of prostate cancer. The administration of exogenous testosterone is not a means of reversing the aging process in men with normal testosterone levels, but it may offer considerable benefit for men suffering from hypogonadism.