Arrhythmogenic Cardiomyopathy (ACM) is a primary disorder of the myocardium characterized by a high propension for ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Several genes have been associated with the development of aggressive forms of ACM, the most common of which is the one encoding for plakophilin-2 (PKP-2). Currently, no disease-modifying treatment for ACM exists and current therapeutic options are limited to implantable cardioverter defibrillator (ICD) for SCD prevention. In recent years, the use of adeno-associated viral vector (AAVV) based gene replacement therapies for the potential treatment of some ACM forms have been proposed with several technologies and related trials in the development pipeline. The main aim of this review is to highlight the state of current AAVV technologies, to summarize the prior experiences with their use in the field of cardiovascular medicine, and to specifically focus on the currently active trials with AAVV technologies in the field of ACM with a great focus on PKP-2 efforts. Side effects associated with AAVV administration, potential caveats associated with immunosuppression and realistic biological and clinical outcomes will be discussed in the review. Hope is to provide data and perspective to clinicians to foster education in these novel technologies and to empower providers in their risk / benefit conversations with patient with ACM interested in pursuing them.