A sociological framework is proposed to better understand how spatial characteristics translate into people's physical and psychosocial conditions that are relevant to their health. In particular, high susceptibility to poor health among specific adult population groups is analyzed in terms of exclusion from or inadequate participation in a society's structure of opportunities. Acquisition of, and agency through, core social roles, such as the work role, the family and marital role, and civic roles, are essential prerequisites for successful personal self-regulation in adult life, strengthening a sense of self-esteem, self-efficacy, and belonging (self-integration). It is argued that exclusion from, or loss of core social roles, threats to their continuity and confinement to non-reciprocal exchange impair personal self-regulation and trigger a state of 'social reward deficiency'. This state, in turn, elicits prolonged stressful experience, and it may reinforce a person's craving for stress-relieving, potentially addictive health-damaging behavior. This framework is applied to the explanation of the life expectancy gap between Western and Central/Eastern European countries. Although most of the epidemiological evidence reviewed in support of this approach originates from investigations that were conducted in western countries several results reported in the collection of articles published in this Special Issue of Social Science and Medicine are in line with the proposed framework.