Women differ from men in their manifestations of ischemic heart disease (IHD). They also differ from men with respect to prevalence of psychosocial factors and vulnerability to specific mental disorders. Young women, in particular, appear to be highly susceptible to the adverse cardiovascular effects of psychosocial stress. Those who already have clinical manifestations of IHD display high psychosocial burden which could affect their prognosis. Thus, psychosocial risk factors, in particular depression, early life stress, socioeconomic disadvantage, and PTSD, may be key in defining a path of vulnerability for IHD early in women’s lives, even if the disease manifests later.