Since the beginning of clinical use in the 1970s, hemoglobin A1c (A1c) has become the standard tool for monitoring glycemic control in patients with diabetes. The role of the A1c test was broadened in 2010, when the American Diabetes Association added A1c as a diagnostic criterion for diabetes. Because of hemoglobin A1c's integral role in diagnosis and treatment, it is important to recognize clinical scenarios and interfering factors that yield false results. The purpose of this review is to describe the A1c measurement, outline clinical scenarios or factors that may yield false results, and describe alternative laboratory biomarkers.