Ozone is a very reactive gas that is toxic to the respiratory system. However, under controlled conditions, it can be therapeutically useful in several human diseases. An unfavourable combination of factors (ozone is one of the worst troposphere pollutants) and past misuse have led to misgivings about ozonetherapy. However, basic and clinical work developed over the past 10 years has clarified the fundamental mechanisms of action of ozone in biology and medicine. Interestingly, judicious doses of ozone dissolved in blood trigger a cascade of well-defined chemical compounds acting on multiple cellular targets according to well-known molecular, biochemical and pharmacological pathways. Ozonetherapy is proving to be very useful in age-related macular degeneration, ischaemic and infectious diseases, and in wound healing disorders, where conventional medicine has failed. Critical evaluation of the potential therapeutic utility of this simple, inexpensive medical application by national and international health authorities is warranted and may lead to clinical benefit for a large proportion of the world's population.