The individual variability of opioid pharmacology suggests that the patients' genetic disposition influences the response to opioids. Given the complexity of morphine pharmacology, variability may be caused by several genes. Data suggest that variability in genes encoding the enzyme metabolising morphine (UGT2B7 gene), mu-opioid receptors (OPRM1 gene) and BBB transport of morphine by multidrug resistance transporters (MDR1 gene) influence the clinical efficacy of morphine. Furthermore, variability in an enzyme-degrading catecholamines (COMT gene) may also alter the efficacy of morphine, which shows that genetic variability in non-opioid systems may indirectly influence the clinical opioid efficacy. Results obtained so far strongly suggest that opioid efficacy is partly related to inborn properties caused by genetic variability.