Opioids are used in clinical practice for sedation, anesthesia, and analgesia. Their effects depend on their pharmacokinetic and pharmacodynamic characteristics. The liver is the major site for the biotransformation of most opioids. The major metabolic pathway is oxidation. Metabolism influences distribution, clearance, onset, and offset of opioid drugs. Action also depends on the coupling of opioids with the class of receptors involved and on localization of specific receptors. Three major types of opioid receptors, designated as μ, ẟ, and ϰ, present in the central nervous system, are coupled to G proteins and inhibit adenylyl cyclase. Down’s syndrome is a congenital condition characterized by mental retardation and particular physical features. Neurotransmission alterations are important. Alteration in the concentration of opioids in the cortex of these patients has been demonstrated. Neurobiological abnormalities and, in some, abnormalities in the neurotransmission systems, anxiety, and, in particular, nociception all suggest that structural and functional alterations of opioid receptors may be present. A clear knowledge of these multiple abnormalities is essential for skillful management of the perioperative period and for a good outcome for patients with Down’s syndrome.