In this article, we review recent advances in our understanding of arrhythmia mechanisms in the failing heart. We focus on changes in repolarization, conduction, and intracellular calcium cycling because of their importance to the vast majority of clinical arrhythmias in heart failure. We highlight recent efforts to combat arrhythmias using gene-based approaches that target ion channel, gap junction, and calcium cycling proteins. We further discuss the advantages and limitations associated with individual approaches.