Problem Development of alternative CD4(+) T cells provides flexibility to the immune system. This is crucial for the initiation of appropriate effector mechanisms to protect against various pathogens such as bacteria, viruses, tumors, and parasites. Method of study Review of research on the epigenetic regulation of T-cell subsets. Results Studies of the epigenetic modulation of T-cell subset function/dysfunction during the past years have increased our understanding of how the alternative effector populations arise and how their identity is maintained during clonal expansion. Conclusions The recent advances in epigenetic research within the field of immunology have also raised questions on how immunology is regulated during pregnancy and early life and how epigenetic regulation of the immune system during prenatal development is related to diseases later in life such as autoimmunity and allergy.