Recombinant adeno-associated virus (rAAV) can be delivered to the skeletal muscle of the limb (pelvic or thoracic) by means of regional intravascular delivery. This review summarizes the evolution of this technique to deliver rAAV either via the arterial blood supply or via the peripheral venous circulation. The focus of this review is on applications in large animal models, including preclinical studies. Based on this overview of past research, we aim to inform the design of preclinical and clinical studies.