Diabetes can strike at any age, from childhood to adulthood, and lasts a lifetime. Thus, it is important to find ways to increase the quality of life for diabetic patients through intensive, continuous care of blood glucose concentrations. Glucose biosensors that are implanted under the skin are promising for continuous glucose monitoring because they can constantly read blood glucose concentrations and signal a warning in case of hypo- or hyperglycemia. The demand for subcutaneous glucose biosensors has led to the development of many glucose-sensing principles and sensor designs. This Review covers the effort to develop subcutaneous glucose biosensors, including the glucose-sensing principles, and discusses their current status for in vivo monitoring. In addition, the Review examines the future prospects for intensive diabetes care.