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. We review data which shows that variability in genes coding the enzyme metabolizing morphine (UGT2B7 gene), mu-opioid receptors (OPRM gene) and blood-brain barrier (BBB) transport of morphine by multidrug resistance transporters (MDR1 gene) influences the clinical efficacy of morphine. Furthermore, variability in an enzyme degrading catecholamines (COMT gene) alters the efficacy of morphine demonstrating that genetic variability in non-opioid systems may indirectly influence the clinical efficacy from morphine. Thus, results obtained so far strongly argue that opioid efficacy is partly related to inborn properties caused by genetic variability.