Repressive epigenetic modifications such as dimethylation and trimethylation histone H3 at lysine 9 (H3K9me2 and H3K9me3) and H3K27me3 have been shown to be critical for embryonic stem (ES) cell differentiation by silencing cell lineage‐promiscuous genes. CD4⁺ T helper (T_H) cell differentiation is a powerful model to study the molecular mechanisms associated with cellular lineage choice in adult cells. Naïve T_H cells have the capacity to differentiate into one of the several phenotypically and functionally distinct and stable lineages. Although some repressive epigenetic mechanisms have a critical role in T_H cell differentiation in a similar manner to that in ES cells, it is clear that there are disparate functions for certain modifications between ES cells and T_H cells. Here we review the role of repressive histone modifications in the differentiation and function of T_H cells in health and disease.