Cardiovascular disease (CVD) is the leading cause of death among women in the United States. A large proportion of deaths attributable to CVD occur in asymptomatic women, making early detection and diagnosis difficult. As a result, women tend to be diagnosed at later stages of disease when compared with men. In addition, women have not experienced as great a decline in CVD mortality in recent decades as have men. Therefore, the development of primary CVD prevention strategies to decrease the CVD risk in women has become a major public health priority and creates the need for alternate strategies to be developed to decrease CVD risk in women. The success of a nonpharmacological, lifestyle approach for primary CVD prevention has recently been demonstrated in perimenopausal to early postmenopausal women. Two clinical trials, the Women’s Healthy Lifestyle Project (WHLP) and Women On the Move through Activity and Nutrition (WOMAN) study, examined the role of lifestyle to prevent unfavorable CVD risk factor changes that typically occur as a woman transitions through menopause. In both studies, a lifestyle intervention approach, with modest dietary restrictions and increased leisure physical activity, was effective for weight loss and/or weight maintenance and CVD risk factor reduction. More research is needed to determine the long-term benefits of a lifestyle intervention to prevent CVD in women. The existing evidence suggests that the promotion of healthy lifestyle practices by health care providers is a valuable strategy for CVD risk factor reduction in women transitioning through menopause.