Early life environmental events have persisting effects on tissue structure and function, a phenomenon called 'developmental programming'. Exposure to stress and its glucocorticoid hormone mediators may underpin many such effects. Indeed, studies in animal models and observations in humans suggest that prenatal stress/glucocorticoid overexposure causes permanent cardiometabolic, neuroendocrine and behavioural effects in offspring. Such effects appear mediated via tissue-specific changes in gene expression. Underlying epigenetic changes in target gene promoters may ensure persistence of altered transcription long after the initial challenge. Posttraumatic stress disorder and other affective diseases may both act as environmental challenges if present in early life and may themselves be more likely in individuals made 'vulnerable' by early life stress.