Research in social epidemiology suggests that the absence of positive social relationships is a significant risk factor for broad-based morbidity and mortality. The nature of these social relationships and the mechanisms underlying this association are of increasing interest as the population gets older and the health care costs associated with chronic disease escalate in industrialized countries. We review selected evidence on the nature of social relationships and focus on one particular facet of the connection continuum – the extent to which an individual feels isolated (i.e., feels lonely) in a social world. Evidence indicates that loneliness heightens sensitivity to social threats and motivates the renewal of social connections, but it can also impair executive functioning, sleep, and mental and physical well-being. Together, these effects contribute to higher rates of morbidity and mortality in lonely older adults.