The efficacy of first-line therapeutic agents for postherpetic neuralgia (PHN) has been established in randomized, controlled clinical trials. However, pain in PHN is often refractory to treatment. Many of the patients with PHN are elderly, with additional issues of polypharmacy and comorbidity. They experience various types of pain, suggesting that more than 1 pathophysiologic pain mechanism is involved. PHN adversely affects health-related quality of life. Up to this point, no single best treatment has been identified for PHN. Pharmacological treatments for PHN are inadequate, and many patients are undertreated. Suboptimal treatment can be related to intolerable side effects of medications, long titration periods to reach the effective dosage, inadequate dosing, poor compliance with dosing schedules, and low treatment satisfaction. Inadequate therapeutic response leads more than half the patients with PHN treated with either gabapentin or pregabalin to switch to another class of medication, and more than 30% of patients to add on another class of medication. Safety and tolerability are important considerations in therapy, especially in the elderly. Few patients with PHN and physicians are satisfied with the currently available treatments. Thus, the effective management of postherpetic neuralgia remains an ongoing challenge. New and improved treatment options are therefore needed for the effective management of PHN.