Women in mid-life experience unique stressors, including transitions within their family roles, informal caregiving, job stress, and perceived discrimination. The impact of these stressors on cardiovascular health in women during mid-life is of growing interest in both the popular and scientific literature. The objective of this review is to summarize the recent literature on stress and cardiovascular health in mid-life women. We focus on stressors that are relevant to mid-life women, including social stress and discrimination, and long-term risk of CVD events and subclinical CVD measures. We systematically reviewed the literature published between January 2012 and April 2018 for studies examining stress in mid-life and either CVD endpoints or subclinical CVD outcomes. Eligible studies included at least one psychosocial stress exposure, a CVD or subclinical CVD outcome, and either included only female participants, reported sex-stratified analyses or tested for a sex*stress interaction. We identified 37 studies published since 2012 that met our criteria and included women between the ages of 40 and 65, including 3 case-control studies, 15 cross-sectional studies, and 19 prospective cohort studies. Because clinical CVD events typically occur after age 65 in women, only 22 studies were available that evaluated stress and hard CVD events in samples with mid-life women. Results from these studies suggested an increased and significant risk of CVD due to stress. Of the 15 studies that included subclinical CVD outcomes, the majority showed that mid-life women experiencing greater levels of stress had more subclinical CVD, as indicated by carotid intima-media thickness, flow-mediated dilation and arterial stiffness; however, several studies reported null associations. General life stress, including perceived stress and life events, in mid-life was significantly related to later-life CVD risk and mid-life subclinical CVD in the majority of studies published in the past six years. Job stress was inconsistently related to CVD risk in women, and fewer studies examined characteristics of other social roles, such as marriage, motherhood or caregiving. Perceived discrimination also was associated with CVD events and subclinical CVD in some samples of mid-life women. Further investigation into specific stressors relevant to women in mid-life, including caregiving and marital stress, are needed to understand the full extent to which life stress impacts CVD risk in mid-life women.