The NF-κB family of inducible transcription factors is activated by various stimuli, with members of the TNF cytokine family being among the best-characterized inducers. Over 25 years of research have shown a strong connection between NF-κB and TNF. Knockout mice unable to activate NF-κB die embryonically, but deletion of TNF or TNFR1 rescues this lethality, highlighting NF-κB's role as a key regulator of TNF responses. The physiological connections between NF-κB and TNF cytokines are numerous, with the canonical and noncanonical pathways being the main focus of this review. The canonical pathway involves the degradation of IκBα, while the noncanonical pathway involves the processing of p100 to p52. The regulation of these pathways by TNF family signaling is discussed, with a focus on TNFR1 and CD40 signaling. IKK kinases, including IKKα and IKKβ, play a crucial role in NF-κB activation, with NEMO being essential for the canonical pathway. TRAF proteins, such as TRAF2, are involved in the recruitment of IKK complexes and the activation of NF-κB. The noncanonical pathway is regulated by NIK, which is phosphorylated and activated by the NF-κB inducing kinase. TRAF3 is involved in the constitutive degradation of NIK, while TRAF2 and cIAP1/2 are required for inducible NIK accumulation. The review also discusses the termination of NF-κB responses through negative feedback loops, including the induction of IκB transcription and the role of A20 in regulating NF-κB activity. The role of CD40 signaling in the noncanonical NF-κB pathway is also discussed, with a focus on the activation of NIK and the processing of p100 to p52. Overall, the review highlights the complex interplay between TNF family cytokines and NF-κB signaling, with a focus on the regulation of the canonical and noncanonical pathways.The NF-κB family of inducible transcription factors is activated by various stimuli, with members of the TNF cytokine family being among the best-characterized inducers. Over 25 years of research have shown a strong connection between NF-κB and TNF. Knockout mice unable to activate NF-κB die embryonically, but deletion of TNF or TNFR1 rescues this lethality, highlighting NF-κB's role as a key regulator of TNF responses. The physiological connections between NF-κB and TNF cytokines are numerous, with the canonical and noncanonical pathways being the main focus of this review. The canonical pathway involves the degradation of IκBα, while the noncanonical pathway involves the processing of p100 to p52. The regulation of these pathways by TNF family signaling is discussed, with a focus on TNFR1 and CD40 signaling. IKK kinases, including IKKα and IKKβ, play a crucial role in NF-κB activation, with NEMO being essential for the canonical pathway. TRAF proteins, such as TRAF2, are involved in the recruitment of IKK complexes and the activation of NF-κB. The noncanonical pathway is regulated by NIK, which is phosphorylated and activated by the NF-κB inducing kinase. TRAF3 is involved in the constitutive degradation of NIK, while TRAF2 and cIAP1/2 are required for inducible NIK accumulation. The review also discusses the termination of NF-κB responses through negative feedback loops, including the induction of IκB transcription and the role of A20 in regulating NF-κB activity. The role of CD40 signaling in the noncanonical NF-κB pathway is also discussed, with a focus on the activation of NIK and the processing of p100 to p52. Overall, the review highlights the complex interplay between TNF family cytokines and NF-κB signaling, with a focus on the regulation of the canonical and noncanonical pathways.