Life-course view of noncommunicable disease (NCD) risk. Risk increases in a nonlinear way as a result of declining plasticity and accumulative damage from lifestyle-imposed or other challenges. The effect of mismatch between developmentally and evolutionarily influenced phenotype and adult environment also increases through the life-course. Interventions in adults, especially those at high risk, can be beneficial, but only to a degree. Screening in middle-aged adults may also be too late to reduce risk substantially. Interventions in adolescents and young adults are likely to be more effective and, importantly, can reduce the risk of NCDs in the next generation. The prenatal period establishes risk through interaction between genetic, epigenetic and environmental factors. (From Hanson and Gluckman 2014, Physiology Review 94: 1027–1076, with permission.)