Transforming growth factor β‐activated kinase 1 (TAK1) is a key regulator of the innate immunity and the proinflammatory signaling pathway. In response to interleukin‐1, tumor necrosis factor‐α, and toll‐like receptor agonists, it mediates the activation of the nuclear factor κB (NF‐κB), c‐Jun N‐terminal kinase (JNK), and p38 pathways. In addition, TAK1 plays a central role in adaptive immunity, in which it mediates signaling from T‐ and B‐cell receptors. This review will focus on recent developments and also examine the regulation of TAK1 in response to a diverse range of other stimuli including DNA damage, transforming growth factor‐β, Wnt, osmotic stress, and hypoxia. © 2012 IUBMB IUBMB Life, 2012, 64(10):825–834, 2012