Nuclear factor-kappaB (NF-kappaB) is a transcriptional factor that was originally discovered in the nucleus of B cells that bind to the kappa light chain of the immunoglobulins. Research during 15 years, however, has revealed that NF-kappaB is present in its inactive state in the cytoplasm of almost every cell type. When activated, NF-kappaB translocates to the nucleus, binds the DNA and regulates the expression of over 200 different genes. The product of these genes regulate the immune system, cell proliferation, tumor metastasis, inflammation and viral replication. Several tumor cell types express constitutively activated form of NF-kappaB and it is required for the proliferation of the tumor cells. Numerous studies have shown that Hodgkin's disease cells exhibit constitutive active NF-kappaB. The present review examines the mechanism how NF-kappaB is activated and its relevance to Hodgkin's disease.