After activation, CD4+ helper T (Th) cells differentiate into cytokine-secreting effector subsets. A novel subset of CD4+ helper T (Th) cells that produce two related cytokines IL-17 and IL-17F has been recently identified and shown to play critical function in inflammation and autoimmunity. Here I summarize recent work by us as well as other investigators in understanding the transcriptional regulation of Th17-cell differentiation, their developmental relationship with regulatory T cells and the function of IL-17 and IL-17F in vivo.