Antiretroviral-associated toxicity, especially in the case of tenofovir plus boosted protease inhibitors, could affect different functions of the proximal renal tubule. Considering the long-term use of antiretroviral therapy and the concomitant presence of other risk factors, several degrees of proximal tubular toxicity, from chronic subclinical renal dysfunction to Fanconi syndrome, could be observed in HIV-infected patients. However, the clinical significance of isolated tubular dysfunction, in the short and long term, remains unclear. In addition, primary tubular abnormalities, even severe, may be missed until they affect the glomerular function. Therefore, there is a need for new biomarkers, not only based in serum creatinine and estimated glomerular filtration rates, that might help to identify tubular cell toxicity and predict the clinical outcome in HIV-infected patients. Increased values of urinary beta-2-microglobulin and retinol-binding protein, observed in up to 70% of patients, have been associated to tenofovir-associated mitochondrial dysfunction. Together with other tubular parameters or in isolation, both biomarkers could be useful for diagnosing proximal tubular toxicity. Other molecules, such as urinary kidney injury molecule- 1, neutrophil gelatinase associated lipocalin, or N-acetyl-b-D-glucosaminidase, could help to distinguish between tubular cell damage and dysfunction. Here, we review the current knowledge on tubular toxicity in HIV-infected patients on antiretroviral therapy.