Antigen-primed T cells respond to restimulation much faster than naïve T cells and form the cellular basis of immunological memory. The formation of memory Th2 cells starts when naïve CD4 T cells are transformed into effector Th2 cells and is completed after antigen clearance and a long-term resting phase accompanied by epigenetic changes in the Th2 signature genes. Memory Th2 cells maintain their functions and acquired heterogeneity through epigenetic machinery, on which the recall-response of memory Th2 cells is also dependent. We provide an overview of the epigenetics in the whole Th2 cell cycle, mainly focusing on two different histone lysine methyltransferase complexes: the Polycomb and Trithorax groups. We finally discuss the pathophysiology and potential therapeutic strategies for the treatment of Th2-mediated inflammatory diseases in mice and humans.