Neuropathic pain, or pain after nervous system injury, can be very refractory to pharmacologic interventions. Through a better understanding of the pathophysiology of neuropathic pain, it has been suggested that nonopioid agents, such as antidepressants and anticonvulsants, may be more efficacious in the treatment of neuropathic pain than common analgesics, such as opioids or nonsteroidal anti-inflammatory drugs. However, this has not been consistently demonstrated in clinical studies. Conversely, many confounding factors of neuropathic pain make it difficult to interpret clinical studies. Therefore, we must develop a better understanding of the preclinical models of neuropathic pain to better understand the application of new and old drugs to the human neuropathic pain state. This article provides an overview of the commonly used preclinical neuropathic pain models, followed by a summary of the efficacy of currently available agents in preclinical pain models and human correlates.