This article reviews the history of the use of antidepressants in painful states and traces the evolution of thinking from initially considering them as antidepressants to the current concept that they have an analgesic action. The greatest part of this paper considers chronic, nonmalignant, painful states and the evidence with each for the efficacy of some of these drugs. The mechanism of action, pharmacokinetics and adverse effects are discussed. Practical suggestions are made regarding their usage. Although antidepressants are imperfect analgesics because of limited efficacy and untoward effects, they may be the only avenue of relief for a painful condition. The correct choice of agent and proper administration are critical.