Population-based studies of health typically focus on psychosocial contributors to illness and disease. We examine findings from a national longitudinal study of American adults, known as MIDUS (Midlife in the U.S.) to examine the role of psychosocial factors in promoting resilience, defined as the maintenance, recovery, or improvement in health following challenge. Classic studies of resilience are briefly noted, followed by a look at three categories of resilience in MIDUS. The first pertains to having good health and well-being in the face of low socioeconomic standing. The second pertains to maintaining good health and well-being despite the challenges that accompany aging. The third pertains to resilience in the face of targeted life challenges such as abuse in childhood, loss of spouse in adulthood, or having cancer. Across each area, we summarize evidence of positive health, and where possible, highlight protective influences that account for such salubrious outcomes. We conclude with opportunities for future research in MIDUS such as examining cultural and genetic influences on resilience as well as utilizing laboratory challenge data to illuminate underlying mechanisms.