Adenoviruses have long been identified as good candidates for use as viral vectors in gene therapy and as vaccines. These viruses can infect multiple cell types, while in division or in quiescence, and are relatively easy to manipulate so that parts of their genome can be replaced with exogenous genes. Progressive safety improvements in replication-deficient adenoviral vectors have been achieved with the second and third generation, and ending with the gutless adenoviral vectors. Adenoviral vectors are immunogenic and can act as adjuvants. Nonetheless, the potency of human recombinant adenoviral vaccines was below expectations in clinical trials mainly because of the pre-existing adenoviral immunity found in the general population. This drawback can however become advantageous in animal health, as no previous immunity to human adenoviral vectors exists in animals. Other viral vectors viruses are used as vaccine, but adenoviruses remain the most employed and promising recombinant vector in veterinary medicine. In this chapter, we review the generation of adenoviral vectors, the immune response they trigger, and their advantages and disadvantages for veterinary use in terms of safety and efficacy. This chapter also describes how recombinant adenoviral vectors can be integrated as tools for vaccination and immunomodulation in veterinary medicine.