With the development of highly active antiretroviral therapy, chronic kidney disease has become a prominent cause of morbidity in individuals infected by HIV. Because serum creatinine has significant limitations in this specific population, cystatin C is emerging as a promising biomarker for both the evaluation of glomerular filtration rate (GFR) and the detection of drug-induced kidney injury. Along with renal function, serum cystatin C concentration is associated with several biological parameters such as C-reactive protein, HIV viral load and CD4+ cells count. All these determinants of cystatin C are, however, more or less independent of GFR. Studies evaluating the accuracy of cystatin C for estimating GFR in the setting of HIV infection are scarce and methodology is often questionable (lack of reference method or inadequate statistical analyses). Thus far, data are insufficient to encourage the use of cystatin C or cystatin C-based equations to estimate GFR in the HIV-infected population. Further research is needed to explore the clinical utility of cystatin C in this setting. Beyond the use of cystatin C as a GFR marker, future studies will have to evaluate its role as a predictor of patient outcome, particularly in regard to cardiovascular morbi-mortality.