This review focuses on the general properties of adenovirus vectors and their application to muscle gene transfer. In the prospect of a treatment for Duchenne muscular dystrophy, in vivo expression of the dystrophin gene in animal models remains the main concern. After the presentation of the two partners: adenovirus and muscle, we summarize our results of gene transfer in mice. We have evaluated efficiency of systemic and intramuscular injections, the impact of age at injection, the duration of expression in adult normal and genetically-immunosuppressed SCID mice, using a recombinant adenovirus expressing a reporter gene. After adenovirus-mediated transfer of a mini-model, we have shown an efficient and stable expression of the transgene, a long-term correction of the degeneration process and a functional protection of the treated muscle. The discussion focuses on the problems and the perspectives for gene therapy: safety problems, improvement of safety and vector capacity, host immune response, delivery to muscle and muscle-targeted expression.