Maintaining blood glucose concentration within an acceptable range is a goal for patients with diabetes mellitus. Point-of-care glucose meters initially designed for home self-monitoring in patients with diabetes have been widely used in the hospital settings because of ease of use and quick reporting of blood glucose information. They are not only utilized for the general inpatient population but also for critically ill patients. Many factors affect the accuracy of point-of-care glucose testing, particularly in critical care settings. Inaccurate blood glucose information can result in unsafe insulin delivery which causes poor glucose control and can be fatal. Healthcare professionals should be aware of the limitations of point-of-care glucose testing. This chapter will first introduce glucose regulation in diabetes mellitus, hyperglycemia/hypoglycemia in the intensive care unit, importance of glucose control in critical care patients, and pathophysiological variables of critically ill patients that affect the accuracy of point-of-care glucose testing. Then, we will discuss currently available point-of-care glucose meters and preanalytical, analytical, and postanalytical sources of variation and error in point-of-care glucose testing.