The ability to repair or enhance an individual's genetic make-up provides the sublime opportunity to ameliorate or eliminate many clinical disorders that affect mankind. Gene therapy is thus a revolutionary clinical strategy that may potentially treat an array of genetic and non-genetic diseases, as well as a novel method for drug delivery and vaccination. To these ends, adenovirus vectors are currently the most promising means to deliver specific genes of interest into target cells of the patient. A major limitation of the use of adenovirus vectors in clinical trials, however, is the rapidly induced inflammatory response against these infectious particles. This review aims to describe the cellular and molecular mechanisms involved in the adenovirus-mediated inflammatory response.