Purpose of Review <p>Current treatment strategies for heart failure primarily aim to slow disease progression. In the case of rare genetic disorders with associated cardiomyopathies, management is largely supportive. Gene therapy offers a promising alternative that is potentially curative. This review explores gene therapy strategies, vector selection and relevant molecular targets. We also examine pre-clinical and clinical trials investigating gene therapy in cardiomyopathies.</p> Recent Findings <p>Clinical trials for several genetic disorders—including Danon disease, Fabry disease and Duchenne muscular dystrophy—have demonstrated encouraging results. However, with the use of viral vectors and associated immunogenicity eliciting a strong inflammatory response in some patients, there remains a substantial risk of morbidity and mortality.</p> Summary <p>For rare diseases, gene therapy represents a potentially curative, one-time treatment strategy. As the field advances, further work is required to improve vector technology, reduce immunogenicity, decrease off-target effects and address the associated ethical considerations. </p>