Intracellular signalling pathways have provided excellent resource for drug development particularly in the development of cancer therapeutics. A wide variety of malignancies common in human exhibit aberrant NF-κB constitutive expression which results in tumorigenic processes and cancer survival in a variety of solid tumour, including pancreatic cancer, lung, cervical, prostate, breast and gastric carcinoma. Numerous evidences indicate that NF-κB signalling mechanism is mainly involved in the progression of several cancers which may intensify an enhanced knowledge on its role in disease particularly lung tumorigenesis. This has led to tremendous research in designing a variety of NF-κB antagonists with enhanced clinical applications through different approaches the most common being suppression of IκB kinase (IKK) beta activity. Many NF-κB inhibitors for lung cancer are now under clinical trials. Preliminary results of clinical trials for several of these agents include small-molecule inhibitors and monoclonal antibodies. A few combinatorial treatment therapies are currently under investigation in the clinics and have shown promise, particularly NF-κB inhibition associated with lung cancer.