The interleukin-1 receptor associated kinases (IRAKs) are critically involved in the IL-1R/Toll-like receptor (TLR)-mediated signal transduction processes and therefore regulate cellular innate immune responses. Four IRAK members have been identified in the human genome (IRAK-1, 2, M, and 4), which seem to play distinct roles. Recent studies further suggest that some of the IRAK members may also participate in T cell and B cell signaling and regulate adaptive immunity. Given the critical and complex roles IRAK proteins play, it is not surprising that genetic variations in human IRAK genes have been found to be linked with various human inflammatory diseases. This review intends to summarize the recent advances regarding the biochemical regulations of various IRAK proteins and their cellular functions in mediating innate and adaptive immunity.