Cardiovascular disease (CVD) is the primary cause of death in women, and women with type 2 diabetes mellitus are at greater risk of CVD compared with nondiabetic women. The increment in risk attributable to diabetes is greater in women than in men. The extent to which hyperglycemia contributes to heart disease risk has been examined in observational studies and clinical trials, although most included only men or did not analyze sex differences. The probable adverse influence of hyperglycemia is potentially mediated by impaired endothelial function, and/or by other mechanisms. Beyond high blood glucose level, a number of other common risk factors for CVD, including hypertension, dyslipidemia, and cigarette smoking, are seen in women with diabetes and require special attention. Presentation and diagnosis of CVD may differ between women and men, regardless of the presence of diabetes. Recognizing the potential for atypical presentation of CVD in women and the limitations of common diagnostic tools are important in preventing unnecessary delay in initiating proper treatment. Based on what we know today, treatment of CVD should be at least as aggressive in women—and especially in those with diabetes—as it is in men. Future trials should generate specific data on CVD in women, either by design of female-only studies or by subgroup analysis by sex.