Introduction: It is of utmost importance to assess renal function accurately for the proper management of renal failure. Serum creatinine level is used to calculate the creatinine clearance which is used to measure the glomerular filtration rate (GFR) and in grading different stages of chronic kidney disease (CKD). Therefore, the accurate measurement of serum creatinine is of great importance. This review aimed to explain the different methods used in serum creatinine determination and solutions to problems in some of the methods. Methods: A narrative review was conducted with 28 articles searched through the Web searching engine Google Scholar and academic research databases using keywords creatinine, isotope dilution mass spectrometry, high performance liquid chromatography (HPLC), Jaffe reaction, creatinase enzyme and bilirubin. Results: There are different methods available in the determination of serum creatinine level in the medical laboratory sector including isotope dilution mass spectrometry, HPLC, Jaffe reaction and creatinase enzymatic method. Conclusion: Jaffe reaction is the most widely used method to determine serum creatinine levels worldwide. However, this method has several drawbacks and corrective methods are adopted.   Keywords: Creatinine, Isotope dilution mass spectrometry, High Performance Liquid Chromatography, Jaffe reaction, Creatinase method, Bilirubin