The use of adenovirus as a gene transfer vehicle arose from early reports of recombinant viruses carrying heterologous DNA fragments. Adenovirus vectors offer many advantages for gene delivery: they are easy to propagate to high titers, they can infect most cell types regardless of their growth state, and in their most recent embodiments they can accommodate large DNA inserts. In this chapter, the development of adenovirus vectors is reviewed, from the use of so-called first-generation, E1-deleted viruses to the latest generation high-capacity, helper-dependent vectors. Examples of their use in the clinic are described, as are the current areas in which improvements to these vectors are being explored.