Pain is the primary reason that people seek medical care. At present, chronic unremitting pain is the third greatest health problem after heart disease and cancer. Chronic pain is an economic burden in lost wages, lost productivity, medical expenses, legal fees and compensation. Chronic pain is defined as a pain of greater than 2 months duration. It can be of inflammatory or neuropathic origin that can arise following nerve injury or in the absence of any apparent injury. Chronic pain is characterized by an altered pain perception that includes allodynia (a response to a normally non-noxious stimuli) and hyperalgesia (an exaggerated response to a normally noxious stimuli). This type of pain is often insensitive to the traditional analgesics or surgical intervention. The study of the cellular and molecular mechanisms that contribute to chronic pain are of the up-most importance for the development of a new generation of analgesic agents. Protein kinase C isozymes are under investigation as potential therapeutics for the treatment of chronic pain conditions. The anatomical localization of protein kinase C isozymes in both peripheral and central nervous system sites that process pain have made them the topic of basic science research for close to two decades. This review will outline the research to date on the involvement of protein kinase C in pain and analgesia. In addition, this review will try to synthesize these works to begin to develop a comprehensive mechanistic understanding of how protein kinase C may function as a master regulator of the peripheral and central sensitization that underlies many chronic pain conditions.