This handbook provides a comprehensive overview of recent developments in research on the relationship between occupational trajectories over the life course and health. It uncovers the impact of far-reaching changes of work and employment, as evidenced by increased flexibility, discontinuity, and technological innovation, and offers insights into recent theoretical and methodological developments addressing this challenge. In its main parts, it presents the best evidence to readers about the following topics: early life influences on (un)healthy work, chronic exposure to occupational risks; nonstandard employment and poor health; work continuation with chronic disease; occupational determinants of healthy aging. In its final part, it discusses policy implications of current knowledge and points to the need of developing new solutions in research and practice, not least in times of climate crisis and the new pandemic. The important handbook has been prepared by a distinguished editorial team, with chapters written by prominent international experts. Despite its continuous reference to scientific knowledge it addresses its content to a broader, non-specialized readership.