Hemoglobin A1c is the measurement of glycated hemoglobin and can aid in both the diagnosis and continued management of diabetes mellitus. Accurate glycosylated hemoglobin A1c (A1c) measurements are an essential part of decision making in the diagnosis and treatment of type 2 diabetes mellitus. Although national standards exist to eliminate technical error with A1c testing, multiple patient conditions can falsely decrease or elevate the A1c. In this review, we discuss the methods to measure A1c and the corresponding conditions that can affect the clinical utility of the test. Conditions that affect the A1c can be either those that impair erythrocyte production or alter the normal process of glycation. Some variation also has been associated with patient ethnicity and even with normal aging. We describe alternatives to A1c testing for the above clinical scenarios in an effort to make the practicing clinician aware of alternatives for glucose evaluation.