The discovery of the interleukin (IL-)17-producing T cells (TH17) has markedly changed our view of T cell differentiation and T cell-mediated immunity. Characterization of the signaling pathways involved in the TH17 commitment has provided exciting new insights into the contributions of CD4+ T cells to immuno-regulation, host defense, and the pathogenesis of auto-immune diseases. Additionally, emerging data on conversion among polarized T helper cells have raised the question how we should view such concepts as lineage commitment, terminal differentiation, and plasticity of different T cell subtypes. The transcriptional regulatory events and epigenetic modifications that control TH17 cell differentiation are diverse and complex, and despite the intensive efforts on this subject, many questions remain to be answered. In this chapter, we focus on our current understanding of the signaling pathways, molecular interactions, transcriptional events, and epigenetic modifications that result in TH17 differentiation and effector functions.