Gene therapy, developed as an alternative to the use of therapeutic proteins, can be hampered by nuclease degradation of the plasmid DNA, its inability to access target cells, or - when within cells - to enter the nucleus and transfect these efficiently. This text deals with developments in circumventing the problems of direct plasmid administration by the use of viral or non-viral vectors, Representatives from both camps of therapy discuss the challenges and opportunities of the two approaches and present late-20th-century progress with a variety of constructs. These include viruses such as retroviruses, lentiviruses, poxviruses, alphavirus, herpevirus, and parvovirus. Non-viral constructs are represented by polycations, polymers, cationic liposomes and nanoparticles.