Since the mid-1960s, the rate of prime-age American men working or actively looking for work has steadily declined. During this time period, marriage rates have also fallen precipitously, particularly among less-educated groups. A growing body of research has also begun to document a rise in poor health and premature mortality among these populations. These demographic and health-related shifts both reflect and contribute to poverty and economic inequality. Reversing these trends has the potential to improve labor force participation and social well-being as well as boost economic growth. This brief synthesizes current research on work and well-being among less-educated men, many of whom are low-income or poor. It highlights the recent research on labor market characteristics, barriers to work, and family and social ties, and identifies knowledge gaps about why these men’s labor force participation has fallen and how social policy can address this trend.