The cardiac inwardly rectifying potassium channel (I(K1)), which is mainly expressed in mammalian atrial and ventricular myocytes, has been considered as the primary conductance controlling the resting potential (RP) and permitting a significant repolarizing current during the terminal phase of action potential. Therefore, I(K1) is highly influential on the RP, and the modulation of I(K1) would likely have profound effects on cardiac excitability and arrhythmogenesis. This article may shed light on the fundamental properties of cardiac I(K1), the mechanisms of inward rectification and I(K1) subunits composition. Furthermore, the article discusses the role of I(K1) in ventricular excitability and arrhythmogenesis and explores the possibility of modulating I(K1) as an antiarrhythmic mechanism. In fact, both blocking and enhancing I(K1) could be antiarrhythmic, but have proarrhythmic potential at the same time. Action potential duration (APD) prolongation has been accepted as an important antiarrhythmic strategy with some evidence in animal models of arrhythmogenesis that I(K1) blockade can prolongate APD and be antiarrhythmic. However, the potential of I(K1) blockade has not resulted in the development of specific I(K1) blockers used clinically. Safety concerns are probably the main reason, and the therapeutic potential for I(K1) blockers seems somewhat small. On the contrary, the up to date reports indicate that moderately activating I(K1) and hyperpolarizing the RP which has been depolarized by pathologic injury are to be feasible and effective to alleviate some kinds of ventricular arrhythmias.