The treatment of heart failure (HF) may be entering a new era with clinical 
trials currently assessing the value of gene therapy as a novel therapeutic 
strategy. If these trials demonstrate efficacy then a new avenue of potential 
treatments could become available to the clinicians treating HF. In principle, 
gene therapy allows us to directly target the underlying molecular abnormalities 
seen in the failing myocyte. In this review we discuss the fundamentals of gene 
therapy and the challenges of delivering it to patients with HF. The molecular 
abnormalities underlying HF are discussed along with potential targets for gene 
therapy, focusing on SERCA2a. We discuss the laboratory and early clinical 
evidence for the benefit of SERCA2a gene therapy in HF. Finally, we discuss the 
ongoing clinical trials of SERCA2a gene therapy and possible future directions 
for this treatment.