Gene therapy is recently attracting increased attention and cardiac gene therapy is not an exception. Advances in gene transfer vectors, development of new vector delivery methods, and discovery of new gene targets continue to fuel our motivation to use this approach in routine bedside care. In the past two years, we have witnessed important advances in the field, as the results of three recently completed cardiac gene therapy programs have been published. Unfortunately, none of the trials have met their primary efficacy endpoints, but sub-analysis demonstrated potential efficacy. Careful review and interpretation of these trial results will provide important insights and direct us to improve the future trial design. In this review, we update our previous overview with a specific focus on recent clinical trial results. We then contemplate future strategies towards successful application of gene therapy for treating clinical heart failure.