Epidemiological studies have shown that the environment experienced in early life can ‘programme' susceptibility to later disease. Furthermore, there is increasing evidence that these effects can be transmissible to subsequent generations through non-genomic mechanisms, with profound implications for human populations. Several mechanisms can underpin the intergenerational transmission of the programmed phenotype, including persistence of the abnormal environment across generations, maternal effects and the transmission of epigenetic information through the germline. In this review, we discuss the evidence for these mechanisms in human and animal studies and the potential importance of this field for human health.