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In this issue of Current Topics in Medicinal Chemistry, we highlight several aspects of the medicinal chemistry of ion channels and their relevance in drug discovery by collecting comprehensive reviews from several experts working in this field. As pore-forming proteins that regulate ion transport across the membrane on the basis of concentration and electrochemical gradients, ion channels are ubiquitously distributed in the membranes throughout all mammalian cellular life. Since ion channels, such as calcium, potassium and sodium channels, play critical roles in various hereditary, neurological and cardiovascular diseases, they have attracted much attention and are among the most promising classes of targets for drug design and discovery. I would like to express my sincere appreciation to all the authors for their outstanding contributions. I also thank Dr. Allen Reitz, Editor-in-Chief, for inviting me to prepare this special issue of Current Topics in Medicinal Chemistry. Our hope is that this issue will be an informative contribution to the field and will represent a key reference work for those medicinal chemists involved in ion channels.