Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted protease inhibitors (PI/rs), have been associated with increased risk of CKD. However, the CKD risk attributable to these agents is overall small, especially in those with low baseline risk of CKD and normal renal function. CKD risk in HIV-positive individuals can be further minimized by timely identification of those with worsening renal function and discontinuation of potentially nephrotoxic agents. Clinicians can use several monitoring tools, including the D:A:D risk score and routine measurements of estimated glomerular filtration (eGFR) and proteinuria, to identify high-risk individuals who may require an intervention. Tenofovir alafenamide (TAF), a TDF alternative, promises to be safer in terms of TDF-associated kidney and bone toxicity. While the short-term data on TAF does indicate lower eGFR decline and lower risk of proteinuria (vs. TDF), long-term data on renal safety of TAF are still awaited. Promising results have also emerged from recent trials on alternative dual-therapy antiretroviral regimens which exclude the nucleoside(tide) reverse transcriptase class as well as possibly the PI/rs, thereby reducing the drug burden, and possibly the toxicity. However, long-term safety or benefits of these dual-therapy regimens are still unclear and will need to be studied in future prospective studies. Finally, addressing risk factors such as hypertension and diabetes will continue to be important in this population.