The differentiation of Th cells is regulated at different points by antigen and by other factors in a complex fashion that allows impressive flexibility in the T cell response generated and enables close control at multiple points to prevent an unwanted response. Studies over the past two years have uncovered several principles of this regulation, including a new appreciation of the critical role of survival factors in determining the success of the immune response. New insights into the details of CD4(+) T cell regulation will provide important clues as to how immune responses are regulated, in particular the generation of effector responses and development of long-lived immunity.