The practice of off-label prescribing, i.e. prescribing drugs either for unregisteredunapproved therapeutic indications and age groups or using unregisteredunapproved doses or methods of administration, is common in older patients. This may be due to the poor representation of this group in pre-marketing clinical trials assessing therapeutic efficacy and safety of novel therapies or merely to the fact that trials in a particular indication have not been undertaken. Off-label prescribing should not be viewed as scientifically or ethically unsound when there are good clinical data to support a particular therapeutic indication. However, a number of steps should be followed in order to ensure therapeutic efficacy, reducing, at the same time, the risk of adverse drug reactions andor medical litigation. This article discusses the current epidemiology and trends in off-label prescribing in older patients, the scientific and ethical justification of this practice, medico-legal implications, and proposed strategies for risk mitigation.