Testosterone deficiency (TD) is a common condition in men that increases with age. Signs and symptoms of TD include fatigue, low libido, erectile dysfunction, muscle loss, bone density loss, hot flashes, and mood disturbances. Men with signs or symptoms of TD should be screened. Additionally, men at high risk for TD, such as those with HIV or prior chemotherapy, should be screened even in the absence of signs or symptoms. Testosterone should be drawn in the morning using liquid chromatography and mass spectrometry for total testosterone (TT) and equilibrium dialysis for free T (FT). A TT < 300 ng/dL (10.4 nmol/L) is consistent with TD. Patients need a baseline hematocrit level prior to starting testosterone therapy (TTH). All forms of TTH, but especially intramuscular T (IMT) have a risk for polycythemia, so this needs to be monitored closely. While some data has suggested an increase in major adverse cardiac events (MACE) with TTH, these studies all had methodologic flaws which calls the results into question. Meta-analyses of higher quality data show no increased risk of MACE with TTH. Men should be screened for prostate cancer (CaP) before starting TTH. There is no data to suggest that TTH increases CaP risk. Men with TD below the saturation point (<250 ng/dL or 8.7 nmol/L) will likely experience an increase in prostate-specific antigen (PSA) after initiation of TTH. The data suggests no increase in prostate volume or lower urinary tract symptoms (LUTS) in men on TTH. Men need to be counseled on the fact that exogenous T can cause infertility. Men who desire future fertility should be offered alternative therapies such as anastrazole or clomiphene citrate.