Background and Purpose: Pain is an unpleasant warning sensation of imminent damage of the tissue or organ, and is a very frequent reason for patients to seek the physician's help. The aim of this paper is to give an overview on the role of voltage gated sodium channels in nociception and to highlight the mechanisms of the action of local anesthetics in inhibiting conduction of ion currents, thus affecting the sense of pain. Materials and Methods: A comprehensive search of the literature with key words: voltage gated sodium channels (VGSC), nociception, local anesthetics, α, β- subunit isoforms in Medline was conducted. Results: VGSC isoforms Nav1.7, Nav1.8, Nav1.9 are highly expressed in nociceptive neurons and associated with neuropathic pain syndrome. Human studies demonstrated that point mutations of these isoforms, particularly Nav1.7 underlie insensitivity or hypersensitivity to pain. The sodium channel blockers are anesthetics of choice for local analgesia and anesthesia. However, currently available drugs are not considered selective enough and have relatively narrow therapeutic windows, which can limit their usefulness. Isoform – selective pharmacological blockers or gene therapy approaches targeted at down-regulating specific isoforms could show increased therapeutic efficacy for treating pain. Conclusions: Due to restrictive appearance of isoforms Nav1.7 and Nav1.8 in nociceptive neurons, drugs targeting these isoforms would be of great interest, especially in treatment of neuropathic pain syndrome.