Over recent years, our ever-increasing knowledge of the physiological roles of specific ion channel subtypes has led to drug discovery efforts aimed at ion channels of unknown pharmacology. Two of these are the transient receptor potential (TRP) channel TRPV1 and the acid-sensing ion channel (ASIC) family. Drug discovery efforts focused on both of these targets have led to interesting outcomes related to species differences in the mechanism of action of TRPV1 blockers and tissue differences in the physiological roles of the different ASIC subtypes. In addition to the pursuit of novel targets, recent evidence suggests that there are new indications for known channel subtypes and modulators, including pain management for sodium and T-type calcium channel blockers and urinary incontinence for K(ATP) openers.