Sendai virus (SeV), also known as hemagglutinating virus of Japan (HVJ), is a negative-strand RNA virus and a member of the paramyxovirus family. The capacity of SeV to enhance fusion of lipid vesicles and cell membranes was recognized in the early 1980s, and has since been utilized in the form of HVJ-liposomes. More recently, advances in reverse genetics have allowed the construction of a new class of RNA vector with cytoplasmic expression, namely non-transmissible recombinant SeV. Extensive preclinical studies have shown the therapeutic potential of this vector for use in airways, brain and for ischemic diseases and tumors. In addition, the potential of SeV vector for vaccination has been explored. Data on the use of SeV for gene therapy and vaccination since January 2004 are reviewed and recent improvements in SeV vectorology are discussed.