The funny current was first described in the late 70s (Brown et al. 1979) and in the nearly three decades following this early description, its functional role in the generation of spontaneous activity and in the control of cardiac rate has been intensely investigated and firmly established on the basis of a wealth of experimental evidence (DiFrancesco, 1993; Barbuti et al. 2007). In SAN cells, the main determinant of pacemaker rate is the duration of diastolic depolarization. I_f activation at the end of an action potential controls the slope of early diastolic depolarization, and thus determines the duration of diastole by selecting the time after which threshold for a new action potential is reached (Bucchi et al. 2007). I_f is also finely modulated by changes of the intracellular cAMP concentration, a mechanism mediating rate modulation by the autonomic nervous system. I_f activation therefore represents the main physiological mechanism responsible for control of cardiac rate. Not surprisingly, I_f has been the target of active pharmacological research aimed to develop drugs able to control heart rate. Research in this field has led to development of several funny channel-specific drugs, the “heart rate reducing” agents, which work by selective block of funny channels. Ivabradine, the only such compound having passed the required clinical tests, has been shown to slow heart rate without adverse side effects (such as negative inotropic effects). Ivabradine block of funny channels occurs at the cytoplasmic channel side and is “current dependent”, i.e. occurs preferentially when ions flow in the outward direction, while inward current “kicks off” drug molecules from their binding site and relieves block (Bucchi et al., 2002). Since ivabradine is also an “open channel blocker” and thus requires hyperpolarization to gain access to the blocking site, its block is strongly “use-dependent” and becomes more efficient when channels cycle frequently between open and closed states (i.e., during tachycardia). Ivabradine is now marketed as a therapeutical tool against stable chronic angina and is being investigated as a potential tool to reduce morbidity-mortality in CAD patiens with/without heart failure. More recently, other clinically relevant applications of the concept of the funny current-based pacemaking have become apparent. In one example, an inheritable point mutation in the cyclic nucleotide-binding domain of the HCN4 isoform (the main HCN isoform contributing to native funny channels of the sinoatrial node) was shown to cause sinus bradycardia in a large Italian family (Milanesi et al. 2006). The mutation (S672R) behaves as an autosomic dominant mutation and causes the probability curve of heterozygous mutant/wild type HCN4 channels to shift by about 5 mV to the negative direction, thus reducing inward current flow during diastole, which causes a reduced diastolic slope and bradycardia. The more negative position of the activation curve is a constitutive new property of mutated channels and does not alter cAMP-dependent activation. Since acetylcholine has the same effect of shifting the I_f activation curve to the negative direction, the mutation mimics the effects of a mild vagal stimulation. Other mutations affecting funny channel function, and consequently heart rate, may exist, and the one identified may represent just a special case of a more general mechanism for rhythm disorders based on HCN altered function. In another example, the concept of I_f-dependent pacing provides the basic background for the development of newly engineered “biological” pacemakers, whose aim is to eventually replace electronic ones. Techniques used so far for generating biological pacemakers have involved gene-based and, more recently, cell-based approaches, including in situ transfer of HCN2-overexpressing mesenchymal stem cells or transfer of embryonic-stem cell derived spontaneously beating agglomerates. The rationale of these approaches is that funny-channel based pacemaking can be exported to silent cardiac tissue by in situ transfer of I_f-expressing cells. Interest in these recent findings is not simply due to the confirmation of the relevance of funny channels to the control of heart rate, but also to the fact that they provide a background for development of tools useful in the clinical setting. More clinically-relevant tools exploiting funny channel-based pacemaking will likely become available in the near future, in connection with a more detailed knowledge of the basic molecular properties of funny channels function and control.