Voltage-gated sodium channels (Na(V)) are well validated targets for treating pain based both on human genetics and clinical experience. Consequently, there is an extensive literature on sodium channels for the treatment of pain and a number of excellent and thorough reviews have recently appeared; a selection of these is provided. This review does not attempt to evaluate all aspects of the studies in this area, but rather will focuses on several key issues that are incompletely addressed in prior reviews or that represent very recent additions to the literature. Key questions that arise are: 1) How much channel block is required to observe efficacy against neuropathic or inflammatory pain? 2) How can one improve upon the therapeutic index of previously tested Na(V) blockers?