Robust inflammation is one of the most important consequences of necrotic cell death as well as its regulated subtype, necroptosis, both in vitro and in vivo [1], [5], [6], [50], [51]. Our results highlight an important notion that inflammation not only passively accompanies necroptosis in a variety of cellular systems by the virtue of rapid loss of plasma membrane integrity characteristic for necrotic cell death, but also that it is an intrinsic and regulated component of necroptosis due to the specific activation of TNFα synthesis by RIP1/Akt kinases. Therefore, this pathway may represent a new molecular target for the inhibition of pathologic inflammatory signaling. Initial in vivo data appears to support this notion. Two recent papers showed that the loss of control over RIP1/RIP3 kinase activities by FADD and caspase-8 in epithelial cells unleashes a feed forward cycle of necroptosis and TNFα production, resulting in the development of intestinal inflammation in mice and, possibly, in patients with Crohn’s disease [4], [5]. This increased production of TNFα during necroptosis may also be important for acute necrotizing diseases, such as necrotizing pancreatitis and acute bacterial infections, where hyper-acute inflammation accompanying necrotic cell death is the primary cause of multiple organ failure and patient death. Along these lines, another recent paper by Duprez et al. has shown that RIP1 and RIP3 mediate the cellular damage introduced by TNF-induced SIRS [6]. The role of RIP1 kinase in acute and chronic inflammatory diseases warrants further investigation, as efficient and specific RIP1 kinase inhibitors may offer therapeutic benefit for treating these conditions.