In the present review, we argue that social disconnectedness could and should be included in primary-care screening protocols for the detection of cardiometabolic disease. Empirical evidence indicates that weak social connectedness represents a serious risk factor for chronic diseases, including cardiovascular disease, diabetes, and various cancers. Weak social connectedness, however, is largely regarded as a second-tier health-risk factor in clinical and research settings. This may be because the mechanisms by which this factor impacts on physical health are poorly understood. Budding research, however, advances the idea that social connectedness buffers against stress-related allostatic load-a known precursor for cardiovascular disease and cancer. The present paper reviews the empirical knowledge on the relationship between everyday stress, social connectedness, and allostatic load. Of 6022 articles retained in the literature search, 20 met predefined inclusion criteria. These studies overwhelmingly support the notion that social connectedness correlates negatively with allostatic load. Several moderators of this relationship were also identified, including gender, social status, and quality of social ties. More research into these factors, however, is warranted to conclusively determine their significance. The current evidence strongly indicates that the more socially connected individuals are, the less likely they are to experience chronic stress and associated allostatic load. The negative association between social connectedness and various chronic diseases can thus, at least partially, be explained by the buffering qualities of social connectedness against allostatic load. We argue that assessing social connectedness in clinical and epidemiological settings may therefore represent a considerable asset in terms of prevention and intervention.