Testosterone deficiency (TD) is a common clinical condition that causes sexual and non-sexual symptoms. Low serum concentrations of testosterone also predict significant health outcomes, such as diabetes, metabolic syndrome, and increased mortality. Treatment with testosterone therapy (TTh) effectively improves symptoms, and also has a positive impact on body composition and bone density. Since there is no serum testosterone value that reliably identifies men who will respond to treatment from those who will not, healthcare providers must exercise clinical judgment in making the diagnosis of TD. Multiple formulations of TTh are available, each with advantages and disadvantages. Overall, TTh is relatively safe but the risks, such as erythrocytosis, makes long-term monitoring mandatory. The evidence does not support concerns regarding cardiovascular and prostate cancer risks.