Several observational studies have identified tenofovir as an independent risk factor for kidney impairment. Conversely, randomized trials have only demonstrated minor tenofovir-related changes in kidney function, but these studies included patients with normal kidney function and with low underling risk for progression of their renal function, had limited size, and limited follow-up. Several potential mechanisms of tenofovir nephrotoxicity are known. Atazanavir can, equally to indinavir, cause urolithiasis, but both drugs have also been associated with chronic kidney disease (CKD) and fast declining eGFR in persons without clinical symptoms of urolithiasis, especially when the plasma drug concentration is boosted by concomitant ritonavir use. In 2012, only a minority of HIV-positive individuals are affected by drug-induced nephrotoxicity. However, in the future, the clinical impact and hence the requirement for more research in this area will likely increase due to ageing and continued cART exposure of the HIV-positive population.