In the past two decades a large initiative has been put forth to understand the biological and pathogenic properties of the human T-cell lymphotropic virus type 1 (HTLV-1); this has ultimately led to the development of various experimental vaccination and therapeutic strategies to combat HTLV-1 infection. The focus of this work is to outline key targets for the design of therapeutics for HTLV-1, such as fusion mediated by the envelope glycoprotein, and to discuss reports of novel vaccines or therapeutics. These strategies include peptide, recombinant protein, DNA, and viral vectors. The final focus of this review is to acquaint the reader with vaccine approaches developed in our laboratory over the last decade. These strategies include the development of envelope glycoprotein derived B-cell epitopes for the induction of neutralizing antibodies, as well as a strategy to generate a multivalent cytotoxic T-lymphocyte (CTL) response against the HTLV-1 Tax antigen.