Following the discovery of IL-23-dependent T cell immunity, the past decade has witnessed a major revision of the T-helper subset paradigm and substantial progress has been made in deciphering the molecular mechanisms of T cell lineage commitment and function. I will  present our recent work on the transcriptional control of TH17 cell development and highlight the protective vs. pathogenic roles of IL-17 and IL-22 in mucosal tissues. I will also discuss the emerging clinical data showing that antibody-mediated neutralization of IL-17 and IL-23 are remarkably effective for treating immune-mediated inflammatory diseases.