Should renal biopsy be performed in all patients with both HIV infection and kidney disease? In this Viewpoint, Dr Szczech argues that, given its efficacy against conditions like HIV-associated nephropathy, antiretroviral therapy should be implemented before biopsy is considered. Only when suppression of viral replication fails to improve renal function does the case for biopsy become more compelling. In any event, much as with HIV-negative patients with renal disease, empiric therapy should be implemented before renal biopsy is undertaken.