It is widely acknowledged that the nature of the maternal care a child receives can have long-term repercussions, and that children raised in deprived environments can have severe cognitive and behavioural difficulties that last into adulthood. The mechanisms underlying these effects are not understood, but recent data from rodents provide insight into a potential molecular mechanism. Like humans, rodent maternal behaviour towards offspring can effect long-term changes in responses of the offspring to stress throughout the rest of their lives. Remarkably, these changes reflect permanently altered gene expression, so-called “environmental programming”, and its downstream effects on the hypothalamic-pituitary-adrenal axis. This review discusses the nature of this environmental programming–the mechanism by which it occurs in rats, its long-term implications, and opportunities for its reversal in rodents and ultimately in humans.