We provide evidence for multidirectionality, variability, and plasticity in the nature and direction of change in physical health, cognitive functioning, and well-being during the middle years of the life course. The picture of well-being in midlife based on longitudinal data from the Midlife in the United States (MIDUS) study is a more positive one than portrayed in previous cross-sectional studies. We present middle age as a pivotal period in the life course in terms of balancing growth and decline, linking earlier and later periods of life, and bridging younger and older generations. We highlight the role of protective factors and multisystem resilience in mitigating declines. Those in middle age play a central role in the lives of those who are younger and older at home, in the workplace, and in society at large. Thus, a focus on promoting health and well-being in middle age can have a far-reaching impact.