Traditional risk factors for cardiovascular disease (CVD) have long been the focus of preventive strategies. The impact of family stress, depression, anxiety, hostility, pessimism, job strain, social isolation, lack of purpose in life and social support, are well recognized risks for CVD development, however they are under-appreciated in clinical practice guidelines. The purpose of this article is to review the impact of acute and chronic stress on CVD risk, elaborate repositioning in guidelines, with emphasis to approaches for stress reduction. Regular exercise, both aerobic and resistance, leads to better adaptiveness to other types of stress, however, it remains unknown whether the total amount of stress one can receive before negative health effects is unlimited. Evidently, marked reductions in stress related disorders are shown following formal cardiac rehabilitation programs. Attendance of cardiac rehabilitation is highly recommended for the stress-related mortality risk reduction. Innovative approaches to offset the broad challenges that CVD pose, augmented by sustained exposure to stress, are desperately needed, but hindered by a lack of successful population-level interventions that promote lasting change.