NF-κB can be activated in two distinct ways: the canonical and the noncanonical pathway. The noncanonical pathway requires IKKα-dependent processing of NF-κB2 (p100) in the proteasome. The resultant p52 subunit associates with RelB and enters the nucleus to activate transcription. On page 647, You-Sun Kim and colleagues show that the noncanonical NF-κB pathway can also be activated in response to TNFα and describe the events involved its regulation. They identify the receptor interacting protein 1 (RIP1) as a key component of this pathway. The activation of TNF receptor 1 (TNFR1) in the absence of RIP1 leads to a marked decrease in TNF receptor-associated factor 2 (TRAF2) protein levels. This in turn results in stabilisation of the NF-κB-inducing kinase (NIK). The subsequent phosphorylation of IKKα finally leads to increased p100 processing and noncanonical NF-κB pathway activation. RIP1, therefore, not only has a role in the activation of the canonical NF-κB pathway downstream of the TNFR1, but also acts to prevent activation of the noncanonical pathway, thereby having an important role in controlling distinct outcomes in response to TNFα. This is further demonstrated by the observation that, in the absence of RIP1, cells are more sensitive to TNFα-induced cell death at early time points, but protected from further cell death at later stages by activation of the noncanonical NF-αB pathway.