Improved life expectancy among patients with cancer has unfortunately resulted in significant increases in the number of patients experiencing chronic, intractable pain-neuropathic pain syndromes, in particular. Yet treatment for this pain is frequently suboptimal. This is due, at least partially, to the generalized nature of available therapeutics, which are often aimed toward symptom management and temporal pain properties rather than targeted directly toward the multiple mechanisms underlying the generation and propagation of pain. Although the future of pain medicine undoubtedly lies with improved formulations, kinetics, and metabolic characteristics, the current armamentarium nevertheless has proven effective in promoting beneficial outcomes and improved life quality in cancer patients with neuropathic pain. Novel, evidence-based guidelines recommend several agents for first-line consideration, including gabapentin, the lidocaine (5%) patch, tramadol hydrochloride, tricyclic antidepressants, and opioid analgesics. However, in oncology perhaps more than in any other field, pain is dynamic and ever-changing in response to a variety of factors, including chemotherapeutic, radiation, or surgical interventions. For this reason, patient-specific assessment and continual monitoring are warranted when selecting a therapeutic regimen. General considerations, particularly when an opioid agent is utilized, should include pharmacoclinical, pharmacoeconomic, and pharmacogenetic variables.