With the revelation of TLR and related downstream signaling molecules, the field of innate immunity has recently drawn immense interest. Human hosts can specifically react to distinct non-self molecules via innate immunity signaling and illicit highly specific responses (1). TLR-mediated signaling has been shown to control diverse cellular processes including expression of both pro-as well as anti-inflammatory mediators, regulation of cellular apoptosis, as well as cell differentiation. The specificity of TLR signaling is achieved through differential recruitment of adaptor molecules such as MyD88, Mal/TIRAP, TRIF and TRAM. These molecules may subsequently recruit and mediate the activation of IRAK family kinases. To date, four IRAK genes have been identified in the human genome, namely IRAK1, IRAK2, IRAK-M and IRAK4. Initially, it was thought that all IRAKs might play a somewhat redundant role in activating transcription factor NF-κB. As the field evolves, it has been gradually realized that each distinct IRAK may have highly specific downstream target (s), and therefore, contribute to the specific activation of cellular response upon distinct TLR ligand challenge.