Morphine is metabolized into several metabolites, most of them having some pharmacologic activity. The major metabolic pathway of morphine includes formation of glucuronides of morphine: morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in the liver, as well as the formation of minor morphine metabolites (normorphine, codeine, and morphine-3-sulfate). M6G is the most potent morphine metabolite, and its analgesic activity is achieved through direct interaction with opioid receptors. M3G metabolite is characterized by complex pharmacologic activities including partial antagonism of morphine-induced analgesia. The accumulation of M6G (ie, in renal failure) is associated with an increased incidence of morphine-like side effects (ie, respiratory depression, nausea, vomiting), whereas the exact role of M3G and other metabolites is still controversial, but might include development of morphine-resistant pain, allodynia, and tolerance.