Testosterone deficiency syndrome (TDS) is an important problem in andrology practice. The simplest treatment is testosterone replacement therapy (TRT). However, it is important to identify the etiology, the indication for TRT, and to decide the formulation and duration of therapy. It is also important to understand the fertility status and ensure that the prerequisites are met before initiating TRT. There are some specific situations where TRT is contraindicated. Picking the right drug for the right candidate along with lifestyle modifications will yield the best and most consistent results. This chapter deals with how to manage a patient with TDS.