Cardiac K channels are critical determinants of cardiac excitability. In hypertrophied and failing myocardium, alterations in the expression and activity of voltage-gated K channels are frequently observed and contribute to the increased propensity for life-threatening arrhythmias. Thus, understanding the mechanisms of disturbed K channel regulation in heart failure (HF) is of critical importance. Amongst others, Ca/calmodulin-dependent protein kinase II (CaMKII) has been identified as an important regulator of K channel activity. In human HF but also various animal models, increased CaMKII expression and activity has been linked to deteriorated contractile function and arrhythmias. This review will discuss the current knowledge about CaMKII regulation of several K channels, its influence on action potential properties, dispersion of repolarization, and arrhythmias with special focus on HF.