Glucose readings in biosensing often rely on interactions with one of three enzymes: hexokinase, glucose oxidase (GOx), or glucose-1-dehydrogenase (GDH). Among these enzymes, GOx and GDH interactions are commonly used in glucose self-monitoring biosensing. Three detection approaches are available for the electrochemical sensing of glucose, including detecting the amount of consumed oxygen, the amount of hydrogen peroxide produced by enzyme activity, or utilizing a diffusible or immobilized mediator to transport electrons from GOx to the electrode. GDHpyrroloquinolinequinone and GDH-nicotinamide-adenine dinucleotide (NAD) are two frequently utilized GDH-based amperometric biosensor families. Researchers continue to explore ways to improve the performance of these biosensors for enhanced glucose sensing and monitoring in clinical settings.