Despite their many and sometimes life-threatening side-effects, opioids in general and morphine in particular are valuable and potent painkillers. This article describes recent developments in sex-related differences in opioid (morphine) pharmacodynamics, morphine metabolites, the nociceptin/orphanin FQ receptor system, acute opioid tolerance and opioid-induced side-effects, such as opioid-induced respiratory depression and itch, and P-glycoprotein modulation of opioid effect.