BACKGROUND With the increasing prevalence of diabetes, successful management of blood glucose control is increasingly important. Current approaches to assessing glycemia include the use of self-monitoring of blood glucose (SMBG) and hemoglobin A1c (HbA1c). OBJECTIVE To assess the evidence underlying the use of these 2 modalities, to evaluate confounders and sources of error in each test, to describe upcoming developments, and to reach evidence-based conclusions on their optimal use. METHODS Reports identified from MEDLINE searches (1976-2005) using relevant terms were selected for quality and relevance to the stated questions. Particular attention was paid to larger cohort studies, clinical trials, meta-analyses, and established recommendations. RESULTS If used properly SMBG gives an acceptably accurate reflection of immediate plasma glucose levels. Study results vary, but in general, the evidence supports a positive effect of regular SMBG for improving glycemia, particularly in individuals treated with insulin. The best timing of SMBG and its frequency are controversial issues, but the clinical recommendation is for regular monitoring with frequency depending on the treatment and the instability of glycemia. In the relatively near term, SMBG could gradually be replaced by continuous glucose monitoring. HbA1c measures long-term glycemic control, reflecting a time-weighted mean over the previous 3 to 4 months. There are a number of physiologic and methodologic confounders that can affect HbA1c, but standardization of assays has been well established. The main value of HbA1c is its use as a predictor of diabetic complications and the proven effect of improved control of HbA1c on complication risk. A reasonable target value for HbA1c is less than 7%. A new method for measuring HbA1c may cause significant changes in the recommended levels, the numbers reported, and even the name of the test. CONCLUSIONS Assessing glycemia in diabetes can be a challenge, but approaches are available that promote successful management of blood glucose and may thereby lead to a significant reduction in morbidity and mortality related to diabetes.