Having identified teratogenic factors, primary prevention of congenital defects is possible by the implementation of specific measures in pregnant women or those planning pregnancy. Our current understanding of the epigenetic processes acting during reproductive events raises new possibilities to prevent both heritable and sporadic congenital anomalies. Cell differentiation during embryonic-fetal development involves different epigenetic processes which, if altered, may affect either somatic or germ cells. Epigenetic alterations can occur in somatic cells at different stages of life, from fecundation to adulthood, and when germ cells are affected, such changes can even be passed on to future generations. This review summarises the main epigenetic processes that influence gene expression and cell specification at different stages of development. The experimental and epidemiological evidence of environmental agents that cause epigenetic alterations is evaluated, as well as their effects in males and females. As a result, new avenues for primary prevention are proposed.