Drug-induced renal failure is a relatively common event in patients infected with HIV. This group of patients receives a number of potentially nephrotoxic medications for a variety of illnesses. The acyclic nucleoside phosphonates cidofovir and adefovir are antivirals that possess significant nephrotoxicity. Interestingly, tenofovir disoproxil fumurate (DF) is structurally similar to these 2 agents, yet seems to be less nephrotoxic based on a few published studies in HIV patients with intact renal function. We present a case in which acute renal failure developed after therapy with tenofovir DF in a patient with HIV and stable chronic kidney disease.