Botulinum neurotoxin (BoNT) is usually used in physiatric practice in the treatment of spasticity and dystonia. Research involving both animal and human subjects has emerged suggesting potential benefits in painful neuropathic conditions. The animal data strongly support the use of BoNT in the treatment of sensitized pain states. BoNT is probably effective at treating postherpetic neuralgia, probably or possibly effective at treating postoperative/posttraumatic neuropathic pain, and probably effective at treating painful diabetic neuropathy. BoNT's proposed mechanism of action is described as decreasing sensitized nociception in four ways by (1) inhibiting glutamate release in peripheral tissues, (2) decreasing calcitonin gene-related peptide release in peripheral tissue, (3) decreasing transient receptor potential cation channel subfamily V member 1 trafficking to peripheral neuron cell membrane, and (4) decreasing substance P release in peripheral tissue. This review discusses pertinent cellular/animal basic science research in conjunction with clinical research with regard to the role of BoNT in treating neuropathic pain.