Kidney function monitoring using creatinine-based glomerular filtration rate estimation is a routine part of clinical practice. Emerging evidence has shown that cystatin C may improve classification of glomerular filtration rate for defining chronic kidney disease in certain clinical populations and assist in understanding the complications of chronic kidney disease. In this review and update, we summarize the overall literature on cystatin C, critically evaluate recent high-impact studies, highlight the role of cystatin C in recent kidney disease guidelines, and suggest a practical approach for clinicians to incorporate cystatin C into practice. We conclude by addressing frequently asked questions related to implementing cystatin C use in a clinical setting.