To measure creatinine, electrochemical techniques have been coupled with a range of biological recognition elements in a variety of sensor configurations. (To listen to a podcast about this feature, please go to the Analytical Chemistry website at pubs.acs.org/ac.The measurement of creatinine levels in human blood or urine is clinically essential because the levels partially reflect the state of renal and muscle function. Creatinine is naturally produced by the body and is filtered from the bloodstream by the kidneys in relatively constant amounts every day. The normal physiological concentration is 40-150 µM, but it can exceed 1000 µM in certain pathological conditions. Blood levels >150 µM indicate the need to perform tests such as creatinine clearance. Values >500 µM indicate severe renal impairment, ultimately leading to dialysis or transplantation; 1 levels <40 µM indicate decreased muscle mass.The methods most often used for the clinical determination of creatinine are based on colorimetry. 2 However, the methods are affected by numerous metabolites and drugs found in biological samples, such as glucose, fructose, ketone bodies, ascorbic acid, and cephalosporins. 3,4 Introducing enzymes has increased specificity, but the methods also became complicated and less reliable. Large and expensive benchtop analyzers incorporating a number of electrochemical electrodes have been used in central clinical laboratories. Portable and handheld devices incorporating a single-use creatinine biosensor cartridge also have been used.The goal of biosensor engineering in the clinical laboratory setting is to reduce cost, time, and complexity of routine analysis of biological fluids; to enable near-patient testing of blood, urine, and saliva in medical centers; and ultimately to enable home testing by individuals. 5 This article looks at the developments in electrochemical creatinine biosensor research in terms of sensor design and analytical performance on the basis of the recognition element and the nature of transducer. Parameters and specific performance characteristics to consider include cost (<$10/ sensing strip), response time (<1.5 minutes [min]), detection limit (e10 µM), linear range (10-1000 µM), and lifetime (>1 year).