Recombinant adenoviruses have been tested extensively for their potential use as vaccines. They can be engineered to express heterologous proteins, which they present very efficiently to the immune system. Recombinant E1-deleted adenoviruses are safe due to their defect in replication. The comparatively small size of the viral genome furthermore allows for construction of recombinant adenoviruses derived from so-called molecular clones that are propagated in form of plasmid vectors in a bacterial host. This eliminates any risk of an inadvertent contamination with an unknown pathogenic entity that can otherwise readily escape detection if vaccine viruses are exclusively grown in mammalian cell lines. E1-deleted adenoviruses induce excellent immunity upon application to mucosal membranes, suggesting their usefulness as vaccines for infectious agents that enter through the airways, the mucosa of the gut or the genital tract. In the past 15 years, recombinant adenoviruses expressing a variety of antigens have been constructed and tested. Based on the encouraging results, several clinical studies have been undertaken. These promising results are now leading to improved protocols such as prime-boost regimes to elicit broader pathogen-specific cellular and humoral immune responses. Thus far, mainly E1-deleted adenoviral recombinants derived from common human serotypes have been employed as experimental vaccines. Such recombinants have one disadvantage: most humans are naturally infected with these viruses first during childhood and then periodically thereafter. The ensuing virus neutralizing antibodies against structural proteins of adenovirus most notably against the hexon impair the efficacy of adenoviral vaccines based on the homologous serotype. This can be circumvented by the recent development of adenoviral recombinants based on serotypes derived from other species that are closely related to humans such as chimpanzees. This article reviews the main perspectives of adenoviral recombinants that render them attractive for vaccine development.