Late-onset hypogonadism (LOH) is a pathological disorder that develops in males over the age of 40 and is diagnosed upon strict criteria that requires that the individual have total serum testosterone (T) below the normal limits as well as three symptoms of sexual dysfunction. Recommended therapy for young males with hypogonadism is testosterone replacement therapy (TRT). Treatment of LOH with TRT has increased significantly in the past several years, but studies showing adverse risks associated with TRT have led to a growing concern about the safety of such a treatment. This systematic review will give an overview of the pathology of LOH, clinical diagnosis of LOH, and comorbidities associated with this dysfunction. Benefits of TRT in elderly hypogonadal men have included improvement in cardiovascular function, reduced all-cause mortality, increased sexual function, increased bone mineral density, improved body composition, increased muscle strength, improved quality of life, and improvement in metabolic parameters. However, risks associated with TRT have included infertility, worsening lipid panel parameters, polycythemia, increased risk of prostate cancer, and in some cases, increased risk of adverse cardiovascular events.