There are a number of good experimental studies showing that exposure by inhalation to prolonged tropospheric ozone damages the respiratory system and extrapulmonary organs. The skin, if extensively exposed, may also contribute to the damage. The undoubtful strong reactivity of ozone has contributed to establish the dogma that ozone is always toxic and its medical application must be proscribed. Although it is less known, judiciously practiced ozonetherapy is becoming very useful either on its own or applied in combination with orthodox medicine in a broad range of pathologies. The opponents of ozonetherapy base their judgment on the ozone chemistry, and physicians, without any knowledge of the problem, are often skeptical. During the last 15 years, a clear understanding of the action of ozone in biology and medicine has been gained, allowing today to argue if it is true that ozone is always toxic. The fundamental points that are discussed in this paper are: the topography, anatomical and biochemical characteristics of the organs daily exposed to ozone versus the potent antioxidant capacity of blood exposed to a small and precisely calculated dose of ozone only for a few minutes. It is becoming clear how the respiratory system undergoing a chronic oxidative stress can release slowly, but steadily, a huge amount of toxic compounds able to enter the circulation and cause serious damage. The aim of this paper is to objectively evaluate this controversial issue.