Male hypogonadism is associated with potentially distressing adverse effects on diverse organs and tissues. These include sexual dysfunction, particularly diminished libido, as well as mood disturbances, reduced lean body mass, and increased adipose-tissue mass. A wide range of effective and well-tolerated options exists. These include relatively noninvasive therapies, such as testosterone (T) gels and T patches; slightly more invasive treatments, such as the T buccal system; and invasive therapies, such as intramuscular T injections and subcutaneous depot implants (T pellets). Testosterone replacement therapy (TRT) can be individualized to enhance patient health and well-being. Screening and ongoing monitoring are necessary to ensure both the efficacy and safety of TRT, particularly prostate safety. Investigational agents, including selective androgen receptor modulators, may offer new pharmacodynamic and/or pharmacokinetic properties that enhance outcomes of TRT.