Oxygen-ozone therapy, initially started as an empirical approach, has now reached a stage where most of the biological mechanisms of action of ozone have been clarified, showing that they are in the realm of orthodox biochemistry, physiology and pharmacology. Here we have reviewed a few relevant clinical applications and have shown that ozone therapy is particularly useful in cardiovascular disorders and tissue ischemia. In chronic viral infections, it is unable to eliminate the viremia but it may display supportive help by stimulating the immune system. Recently, its use has been successfully extended to the herniated disk pathology and therapy of primary caries in children.