Adenoviruses (Ads) are in the forefront of genetic immunization methods being developed against cancer. Their ability to elicit an effective immune response against tumor-associated antigens has been demonstrated in many model systems. Several clinical trials, which use Ad as vehicle for immunization, are already in progress. Preclinical studies have also demonstrated the efficacy of combining Ad-mediated immunization with adjuvants such as chemotherapeutic agents and cytokines. Issues related to sero-prevalence and safety of Ads, however, continue to pose a challenge and need to be addressed.