Heart failure is a common disease with a poor prognosis. Despite improved therapeutic options, 50% of affected patients have died 5 years after the first symptoms, and more than half of deaths are attributable to malignant arrhythmias. During the recent decade, alterations in excitation-contraction coupling with altered intracellular Ca2+, Na+ and H+ handling has been associated with contractile dysfunction and heart failure progression. Only recently, the role of dysfunctional intracellular ion handling for the induction of triggered arrhythmias has been recognized. The hypothetical concept for triggered arrhythmias in heart failure is an increased diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) into the cytosol with subsequent activation of the sarcolemmal Na+/Ca2+ exchanger. In consequence, a Na+-dependent membrane depolarization during diastole may induce afterdepolarizations, and eventually, triggered arrhythmias. While the concept of triggered arrhythmias in heart failure is now well acknowledged, the pathophysiological stimuli and molecular and cellular alterations that underlie afterdepolarizations are poorly understood. Our experiments will lead to a mechanistic understanding of triggered arrhythmias in heart failure and reveal novel molecular therapeutic targets for this life-threatening disease.