T-cell transformation by the human T-cell leukemia virus type I (HTLV-I) involves deregulation of cellular transcription factors, including members of the NF-kappaB family. In normal T cells, NF-kappaB activation occurs transiently in response to immune stimuli, which is required for antigen-stimulated T-cell proliferation and survival. However, HTLV-I induces persistent activation of NF-kappaB, causing deregulated expression of a large array of cellular genes, which in turn contributes to the induction of T-cell transformation. The HTLV-I transforming protein Tax functions as an intracellular stimulator of IkappaB kinase (IKK), a cellular kinase mediating NF-kappaB activation by diverse stimuli. Tax physically interacts with IKK and renders this inducible kinase constitutively active. By assembling different Tax/IKK complexes, Tax targets the persistent activation of both canonical and noncanonical NF-kappaB signaling pathways. Whereas Tax plays a primary role in HTLV-I-mediated NF-kappaB activation, recent studies reveal that the IKK/NF-kappaB signaling pathway is also activated in freshly isolated adult T-cell leukemia (ATL) cells that often lack detectable Tax expression. The mechanism underlying this Tax-independent pathway of NF-kappaB activation remains poorly understood. Clarifying the precise nature and consequences of the constitutive NF-kappaB activation in ATL cells is important for developing rational therapeutic strategies for this T-cell malignancy.