The pathophysiology of postherpetic neuralgia (PHN) is multifactorial and includes damage to dorsal roots and ganglia due to reactivation of the varicella-zoster virus, peripheral and central sensitization, neuroinflammation involving proinflammatory cytokines and glial activation, as well as disturbances of ascending and descending antinociceptive pathways. Clinical phenotypic variability (pain intensity and quality, allodynia, hyperalgesia, dysesthesias), different dermatomal patterns (including involvement of the ophthalmic branch of the trigeminal nerve), severity of the acute phase, and timing of antiviral therapy initiation determine heterogeneous risks for the development and severity of PHN.