Pain may be undertreated--contributing to anguish, as reported by the World Health Organization. Pain may be overtreated--inadvertently contributing to drug addiction, drug diversion, and even death. Pain may be misunderstood-contributing to illness propagation, as reported in somatization literature. Pain words may even be presented as a tool of manipulation, where report of pain is verbiage in pursuit of utilitarian social consequence. Thus, primum non nocere--first, do no harm--is not easily achieved in the pharmacological treatment of pain, particularly in pain reported chronically. Herein, we examine the pharmacological treatment of chronic pain, and we suggest strategies for improved management that are based on solid principles derived from extensive experience which may protect against the problems derived from the vague and subjective nature of pain symptoms. Optimal treatment of chronic pain may be assisted by three paradigms: (1) an adequate model of appraisal, (2) treatment focused on pathophysiology (whether physical, psychosocial, or some combination of these), and (3) frequent reassessment of total social function. By these approaches, contribution to drug abuse, diversion, and life deterioration can be largely avoided. Whereas the emphasis here is pharmacological management, the principles may be more widely applied to other therapies of chronic pain.