Transcription factors have a profound influence on both the differentiation and effector function of cells of the immune system. T-bet controls the cytotoxicity of CD8(+) T cells and the production of interferon-gamma, and it also affects the development and function of natural killer cells and natural killer T cells. Other factors such as eomesodermin, MEF, ETS1 and members of the interferon-regulatory factor family also contribute to the effector function of immune cells. In this review, we focus on recent studies that have shed light on the transcriptional mechanisms that regulate cellular effector function in the immune system.