People who were small at birth and had poor infant growth have an increased risk of adult cardiovascular disease, osteoporosis, and type 2 diabetes, particularly if their restricted early growth was followed by increased childhood weight gain. These relations extend across the normal range of birth size in a graded manner, so reduced size is not a prerequisite. In addition, larger birth size is associated with risks of obesity and type 2 diabetes. The associations appear to reflect developmental plastic responses made by the fetus and infant based on cues about the environment, influenced by maternal characteristics including diet, body composition, stress, and exercise levels. These responses involve epigenetic processes that modify the offspring's phenotype. Vulnerability to ill health results if the environment in infancy, childhood, and later life is mismatched to the phenotype induced in development, informed by the developmental cues. This mismatch may arise through unbalanced diet or body composition of the mother or a change in lifestyle factors between generations. These insights offer new possibilities for the early diagnosis and prevention of chronic disease.