This Special Issue reprint aims to provide an update on the state of the art and new achievements in the research on altered structure/function relationship in the ion channels involved in neurological diseases’ pathophysiology. Of particular interest are drug screening and targeting, proposing novel therapeutic avenues which can be developed to treat or alleviate mostly incurable diseases. Multi- and inter-disciplinary research contributions, often combining structural, functional, and/or pharmacological approaches with different methods/techniques, are presented.