Treating arrhythmias is a challenge for clinicians because pharmacological therapies are often ineffective or have severe side effects. Patients with heart failure frequently present with supreventricular and ventricular arrhythmias. New antiarrhythmic therapies are needed that modulate the specific pathomechanisms underlying the development of cardiac arrhythmias and may have a better safety-profile. The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies. The current review aims at discussing some novel as well as known cytosolic and sarcolemmal mechanisms involved in CaMKII-dependent arrhythmias without being able to cover all aspects known in the field. This article is part of a Special Issue entitled "Calcium Signaling in Heart".