Never before have we experienced social isolation on such a massive scale as we have in response to coronavirus disease 2019 (COVID-19). However, we know that the social environment has a dramatic impact on our sense of life satisfaction and well-being. In times of distress, crisis, or disaster, human resilience depends on the richness and strength of social connections, as well as on active engagement in groups and communities. Over recent years, evidence emerging from various disciplines has made it abundantly clear: perceived social isolation (i.e., loneliness) may be the most potent threat to survival and longevity. We highlight the benefits of social bonds, the choreographies of bond creation and maintenance, as well as the neurocognitive basis of social isolation and its deep consequences for mental and physical health.