The immune system has the capacity to respond to various types of pathogens including bacteria, viruses, tumors and parasites. This requires a flexible immune system, which in part depends on the development of alternative effector T helper cells, with different cytokine repertoires that direct the overall immune response. The reciprocal effects of the T helper subtypes Th1 and Th2 are well documented, but the mechanisms involved in alternative cytokine expression and silencing are less well defined. Introduction of advances within the field of chromatin folding and epigenetic regulation of transcription has begun to explain some of the fundamental principles of T helper cell development. In addition, epigenetic regulation has proven essential also for the more recently discovered T helper cell subtypes; regulatory T cells and the Th17 lineage. As the importance of proper epigenetic regulation becomes evident, attention is also focused on the potential harmfulness of epigenetic dysregulation. Autoimmunity and allergy are two clinical situations that have been implicated as results of imperfect cytokine silencing. This review will address recent advances in the field of epigenetic regulation of T lymphocytes and their maturation from naive cells into different effector T cell lineages. In particular, epigenetic involvement in regulation of key effector cytokines and specific transcription factors determining the CD4(+) T lymphocyte lineage commitment will be discussed.