This chapter reviews the essential role of ion channels as drug targets in the sensory perception and conduction of pain. Beginning with the role of TRP channels as noxious environmental sensors, the chapter follows the creation of action potentials, their conduction through sodium and potassium channels through to the control of neurotransmitter release at the first synapse by voltage-gated calcium channels. This chapter discusses the therapeutic options that these mechanisms offer and the progress within the drug discovery industry to date.