The Th1/Th2 paradigm has provided the framework for understanding CD4 T-cell biology and the interplay between innate and adaptive immunity for almost two decades. Recent studies have defined a previously unknown arm of the CD4 T-cell effector response--the Th17 lineage--that promises to change our understanding of immune regulation, immune pathogenesis and host defense. The factors that specify differentiation of IL-17-producing effector T-cells from naïve T-cell precursors are being rapidly discovered and are providing insights into mechanisms by which signals from cells of the innate immune system guide alternative pathways of Th1, Th2 or Th17 development.