T-bet was originally described as the key transcription factor defining type 1 T helper (Th) cells. However, it is now clear that it drives the orchestrated generation of effector and memory cells in multiple different lymphocyte lineages. In addition to Th1 cells, CD8 T cells, B cells and some innate lymphocyte populations require T-bet for their development or differentiation in response to antigen. Furthermore, other Th cell populations, including T follicular helper and Th17, as well as regulatory T cells can co-opt T-bet expression to promote functional diversification and colocalization. Thus, T-bet broadly regulates transcriptional programs in response to type 1 inflammatory signals and mediates the coordinated differentiation, function, migration and survival of effector and memory lymphocyte subsets in the affected tissue. Therefore, T-bet expression is essential for effective clearance of pathogens and maintenance of immunity.