The prevalence of diabetes has continued to rise in the Unites States. Diabetes has significant impact on health-related quality of life (HRQOL). Thus, improving HRQOL has been an important aspect of health care management in the diabetic population. In this chapter, we systematically reviewed 20 studies on the correlates of HRQOL in diabetes published between 1998 and 2008. Diabetes-related complications, older age, female sex, black or Native American race/ethnicity, longer duration of diabetes, insulin therapy, obesity, smoking, and physical inactivity are associated with the impairment of HRQOL in diabetes. Micro- and macro-vascular complications appear to be the strongest correlates of HRQOL. Therefore, intervention strategies aimed at preventing or delaying the occurrence of these complications may lead to improvement of HRQOL. Healthy lifestyle habits have been associated with improvement of HRQOL. Because people with diabetes are more likely to be non-smokers and to consume more fruits and vegetables but less likely to reach the recommended level of physical activity than those without diabetes, efforts are needed to promote the adoption of healthy lifestyle habits in order to improve HRQOL in diabetes. As an illustration, we provide updated prevalence estimates of impaired HRQOL among people with diabetes and demonstrate how the healthy lifestyle habits are associated with HRQOL using a large population-based sample.