Human T-lymphotropic virus type 1 (HTLV-1) infection is associated with the clonal expansion and transformation of mature T lymphocytes. While the mechanisms involved are incompletely understood the viral regulatory protein Tax plays a central role in these processes. Recent studies employing genomic and proteomic approaches have demonstrated the marked complexity of gene deregulation associated with Tax expression and confirmed the remarkable pleiotropism of this protein as evidenced by the numerous Tax-cellular protein interactions in infected cells. In this review, we summarize the role of Tax in the deregulation of selected cellular-signaling pathways. Specifically, this has focused on the influence and interaction of Tax with the AP-1 and NF-AT transcription factors, PDZ domain-containing proteins, Rho-GTPases, and the Janus kinase/signal transducer and activator of transcription and transforming growth factor-beta-signaling pathways. In addition to identifying the deregulation of events within these pathways, attempts have been made to highlight differences between HTLV-1 and -2, which may relate to differences in their pathogenic properties.