Although there has been considerable interest in the utilization of gene and cellular therapy for heart disease in recent years, there remain critical questions prior to widespread promotion of therapy, and key among these issues is the delivery method used for both gene therapy and cellular therapy. Much of the failure of gene and cellular therapy can be explained by the biological therapy itself; however, certainly there is a critical role played by the delivery technique, in particular, those that have been adapted from routine clinical use such as intravenous and intracoronary injection. Development of novel techniques to deliver gene and cellular therapy has ensued with some preclinical and even clinical success, though questions regarding safety, invasiveness, and repeatability remain. Here, we review techniques for gene and cellular therapy delivery, both existing and adapted techniques, and novel techniques that have emerged recently at promoting improved efficacy of therapy without the cost of systemic distribution. We also highlight key issues that need to be addressed to improve the chances of success of delivery techniques to enhance therapeutic benefit.