Social isolation and loneliness were already pressing concerns prior to the pandemic, but recent trends suggest a potential broadening of this public health crisis. Social connections have potent influences on health and longevity, and lacking social connection qualifies as a risk factor for premature mortality. However, social factors are often overlooked in medical and healthcare practice. There is also evidence documenting effects on biomarkers and health-relevant behaviors, as well as more proximal means social connection influences physical health. A recent National Academy of Science consensus committee report provides recommendations for how this evidence can inform medical and healthcare. Clinicians play an important role in assessing, preventing, and mitigating the adverse effects of social isolation and loneliness.