Recently, emphasis has been given to the role of the inflammasome in viral infections and, specifically, influenza. NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes are multiprotein complexes containing NLRP3, ASC (or Pycard), and caspase 1. Activation of cytokine/chemokine release through NLRP3 requires a signal derived from Toll-like receptor (TLR) stimulation, with resultant production of pro-IL-1β, -IL-18, and -IL-33. The prointerleukins are in turn cleaved to their respective active forms by caspase 1, which requires the input of an additional signal. The second signal in the context of influenza has been elegantly demonstrated by Ichinohe et al. [31] , who showed that golgi-localized H1N1 M2 is both necessary and sufficient to trigger inflammasome activation. Differential expression of the components of the two signaling cascades that are required for inflammasome activation may therefore explain differences in influenza disease severity. Indeed, mouse knockout studies have shown that intact inflammasomes are necessary for innate immune responses to influenza A, chemokine production, and late stage viral clearance (reviewed in [32] ). Evidence suggests that NLRP3-mediated signaling is also important in cellular recruitment and tissue repair during infection. A similar requirement for proper ASC function was observed in adaptive influenza immune responses. Multiple NLRP3 SNPs have been associated with dysregulated inflammation responses and NLRP3 mRNA stability in humans but have not been examined in the context of pH1N1 susceptibility or mortality [33, 34] (Table 1 ).