Non-communicable diseases (NCD) including cardiovascular disease, diabetes, chronic lung disease and some forms of cancer now pose an increasing threat to global health and the economies of both developed and developing countries, where they are now overtaking communicable diseases (1). Not simply diseases of affluence, attempts to reduce their incidence through adult lifestlye are not succeeding (2). Risk of such disease is set in part during early life, when environmental influences including mother’s diet, body composition and exposure to stress, affect the development of her fetus and newborn, establishing its responses to later environmental challenges such as an obesogenic lifestyle. Paternal lifestyle can also produce developmental effects via the sperm. Such parental effects may confer fitness advantage by enabling rapid phenotypic response to an environmental change (3). If the cues which the developing embryo and fetus detect are inaccurate, e.g. unbalanced maternal diet or because nutritional transition occurs between generations through migration or rapid economic improvement, offspring’s responses are mismatched to later environmental challenges, leading to greater risk of NCD. Whilst undernutrition remains an enormous problem throughout the developing world, in both developing and developed societies adverse consequences of over- and under-nutrition co-exist (4). The resulting risk can be transmitted down multiple generations. The consequences affect many aspects of the lifecourse including reproductive health, behavioural, cognitive problems, osteoporosis, sarcopenia and some allergic conditions. Epidemiological, human clinical and basic science research has now indicated underlying mechanisms, many of which involve epigenetic processes (5, 6). These can thus serve as early markers of later risk and they are in principle reversible by dietary, endocrine or pharmacological means. They include DNA methylation, but also changes in histone protein structure and small non-coding RNAs. New evidence is revealing how such processes, which extend beyond imprinted genes, can modify the effects of transcription factors on gene expression and thus responses to later challenges (7). The specific patterns of CpGs methylated can be important, and the regions of importance are not solely in CpG-rich islands. These physiological insights indicate the opportunity for complex social interventions before conception to reduce NCD risk in the next generation.