Dario DiFrancesco has unravelled the role of ion channels in cardiac rhythm. He identified the mixed cation channel, If, the ´funny´ current, in cardiac Purkinje fibres and in the sinus node. He demonstrated its permeability and gating and recorded single channel properties, a major achievement on the smallest conductance channel known. He made important contributions to the molecular biological characterisation of the channel proteins responsible for If and characterised their biochemical and pharmacological regulations. These experiments have been complemented by mathematical and modelling analyses demonstrating the role of If in pacemaker rhythm. Recently, a selective blocker of this current has been developed (Ivabradine, Servier) which is proving highly efficacious in the treatment of ischemic heart disease by reducing cardiac frequency (and hence metabolic demand). DiFrancesco´s work is an exemplary case of development all the way from molecular mechanisms, through integrative reconstruction, to clinical use of a completely new therapeutic agent.