Low testosterone levels are frequently observed among men with treated and untreated HIV infection. However, the interpretations of biochemical measurements of testicular function are challenging and need to be considered in the context of the clinical presentation and scenario. The distinction between primary and secondary hypogonadism and determination of the underlying clinical pathophysiology are not always straightforward. Early recognition of clinical hypogonadism and appropriate treatment may improve clinical outcomes and quality of life for affected individuals. A principal aim of testosterone replacement is to maintain serum testosterone concentrations in the normal physiological range and should be considered in clinically symptomatic patients.