The discovery that the nature of cytokine production by CD4+ T lymphocytes could drastically alter an immune response led to the categorization of distinct helper T cell subsets, most notably Th1 and Th2. Recent evidence suggests that such helper responses are actually quite heterogeneous and ultimately, the course of an immune response depends upon the predominance of particular cytokines. While the factors leading to the production of individual cytokines are not completely defined, it is clear that the nature and dose of antigen, location of antigen challenge, and genetic composition of the individual all play a role in the process. Elucidating the cellular and molecular pathways responsible for helper T cell differentiation will ultimately permit the manipulation of immune responses to pathogens, as well as the development of novel vaccine strategies.