With evolving knowledge in molecular and cellular cardiology, cardiac gene therapy has already been investigated in clinical studies. Different vector systems for cardiac gene therapy have been developed in recent years. While non-viral vectors, such as plasmid DNA, allow remarkable organ specificity, they are often limited by low transfection efficiency and transient gene expression. In contrast, adenoviral or adeno-associated virus-based vectors transfer the transgene more efficiently, but organ specificity may be reduced and immunogenic properties can limit their applicability. Using advanced transcriptional and transductional targeting strategies, viral vectors have been improved in the last few years. Recently, more efficient serotypes of adeno-associated viruses have been identified that show increased transduction rates, thus reducing the necessity for high virus titers. Combination with specific application techniques, such as intramyocardial injection, catheter-based perfusion, ultrasound targeted microbubble destruction, or retroinfusion may further enhance vector efficiency. This review article will give a broad overview of different gene delivery strategies that have been applied in experimental and clinical studies targeting the heart.