In the normal heart, impulses are generated from the sinoatrial node. It is generally accepted that the pacemaker current, I(f), plays a major role in the spontaneous rhythmic activity. Recently, several electrophysiological and molecular data demonstrate that I(f) channels are present in embryonic and post-natal ventricular myocytes and undergo a downregulation during maturation. Interestingly, the I(f) current is re-expressed in some pathological conditions such as cardiac hypertrophy and heart failure. In these conditions, the overexpression of f-channels is a consequence of electrophysiological remodeling and may represent an arrhythmogenic mechanism in heart failure, a condition associated with high risk for sudden cardiac death. For its physiological and pathophysiological role and the availability of selective f-channel blockers, I(f) may be a suitable therapeutic target in heart failure.