Cystatin C (Cys-C) is a low-molecular weight (13 kDa) protein that is a member of the cysteine protease family and is produced by all nucleated cells. In normal conditions, serum Cys-C is almost completely filtered by the renal glomerulus and largely catabolized by proximal tubular cells. Since serum Cys-C levels are closely correlated with the glomerular filtration rate (GFR), serum Cys-C assay has been introduced as a marker of renal function in patients with kidney diseases. In this review, we focus on studies reported during the past decade in which serum Cys-C levels have been compared to serum creatinine levels as a marker of GFR in pediatric populations. All but one of these studies showed diagnostic superiority or equivalence of serum Cys-C levels vs serum creatinine levels in children. The recent evidence from clinical trials generally supports the use of serum Cys-C assays as a renal function test in pediatric patients. However, clinicians should be cognizant of extrarenal conditions and pharmacological factors that can influence the results of serum Cys-C assays.