Adolescence is a time of physical, cognitive, social, and emotional development. This period is a very sensitive developmental window; environmental exposures, the development of health behaviours (eg, smoking and physical activity), and illness during adolescence can have implications for lifelong health. In the UK and other high-income countries, the experience of adolescence has changed profoundly over the past 20 years. Smoking, drug use, and alcohol consumption have all been in long-term decline. At the same time, obesity and mental ill health have increased and are now common among adolescents, with new risks (ie, vaping, psychoactive substances, and online harms) emerging. In this Viewpoint, we describe these and related trends in England and the UK. Although previous work has explored these changes in isolation, in this Viewpoint we consider them collectively. We explore what might be driving the changes and consider the implications for practice, policy, and research.