Midlife—that is, the ages of 40 to 55—is a pivotal period for preventive care and promoting public health. It is pivotal yet underutilized because it is not recognized as a turning point in maintaining good health. Other life stages are much better defined: early childhood, adolescence, young adulthood, and later, middle age and older adults. This special issue presents the current state of scientific knowledge on the determinants and health status of people aged 40–55. It then explores what can be implemented to benefit the health of people in their 40s and 50s, those who are “invisible” in prevention and public health frameworks. Several innovative programs and initiatives aimed at improving the health of people in this age group are reviewed. Some thirty scientists and practitioners in the field contributed to this special issue. What is striking in this assessment is the widening of social health inequalities: already by midlife, depending on their living conditions, there is a considerable gap between those who have benefited from favorable conditions and, conversely, those whose life course has been much harsher and whose health is already impaired.