This review focuses on the recent advances in understanding the transcriptional control of Th17 cell plasticity and stability, as well as the effector functions of Th17 cells, particularly the role of IL-17 signaling in mesenchymal and barrier epithelial tissues. It also discusses the emerging clinical data showing that anti-IL-17 and anti-IL-23 treatments are remarkably effective for many immune-mediated inflammatory diseases. The discovery of interleukin-23 (IL-23) and the subsequent elucidation of its biology have led to significant insights into immunology. IL-23 plays a crucial role in autoimmunity by inducing a unique inflammatory gene signature in T helper (Th) cells, leading to the identification of a novel subset of Th cells known as Th17 cells. The review highlights the roles of cytokines that promote the development and stabilization of Th17 cells via complex transcriptional networks, and discusses the unique signaling mechanisms of IL-17 compared to other receptor families. Additionally, it explores the disease settings where anti-IL-17 and anti-IL-23 therapeutic agents have shown both expected and unexpected effects. The review also delves into the transcriptional control of Th17 cells, the plasticity versus stability of Th17 cells, and the signal transduction of IL-17. Finally, it discusses the therapeutic potential of targeting the Th17 pathway in various diseases, including psoriasis, Crohn's disease, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.This review focuses on the recent advances in understanding the transcriptional control of Th17 cell plasticity and stability, as well as the effector functions of Th17 cells, particularly the role of IL-17 signaling in mesenchymal and barrier epithelial tissues. It also discusses the emerging clinical data showing that anti-IL-17 and anti-IL-23 treatments are remarkably effective for many immune-mediated inflammatory diseases. The discovery of interleukin-23 (IL-23) and the subsequent elucidation of its biology have led to significant insights into immunology. IL-23 plays a crucial role in autoimmunity by inducing a unique inflammatory gene signature in T helper (Th) cells, leading to the identification of a novel subset of Th cells known as Th17 cells. The review highlights the roles of cytokines that promote the development and stabilization of Th17 cells via complex transcriptional networks, and discusses the unique signaling mechanisms of IL-17 compared to other receptor families. Additionally, it explores the disease settings where anti-IL-17 and anti-IL-23 therapeutic agents have shown both expected and unexpected effects. The review also delves into the transcriptional control of Th17 cells, the plasticity versus stability of Th17 cells, and the signal transduction of IL-17. Finally, it discusses the therapeutic potential of targeting the Th17 pathway in various diseases, including psoriasis, Crohn's disease, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.