Successful gene therapy requires not only the identification of an app
ropriate therapeutic gene for treatment of the disease, but also a del
ivery system by which that gene can be delivered to the desired cell t
ype both efficiently and accurately. Reductions in accuracy will inevi
tably also reduce efficiency since fewer particles will be available f
or delivery to the correct cells if many are sequestered into nontarge
t cells. In addition, the therapy will have net benefit to the patient
only if gene delivery is sufficiently restricted such that normal cel
ls are left unaffected by any detrimental affects of bystander cell tr
ansduction. Here we review how currently available delivery systems, b
oth plasmid and viral, can be manipulated to improve their targeting t
o specific cell types. Currently, targeting is achieved by engineering
of the surface components of viruses and liposomes to achieve discrim
ination at the level of target cell recognition and/or by incorporatin
g transcriptional elements into plasmid or viral genomes such that the
therapeutic gene is expressed only in certain target cell types. In a
ddition, we discuss emerging vectors and suggest how gene therapy deli
very systems of the future will be composites of the best features of
diverse vectors already in use.