Ozone is an antiseptic, immune-modulator, analgesic, and antiinflammatory gas with an unstable and powerful oxidizing effect. In biological media, ozone rapidly turns into oxygen and oxygen radicals, creating a moderate oxidative stress. Ozone is perceived as an oxidative threat in the body. This results in activation of the enzymes working in antioxidant defense mechanisms. Ozone application can be evaluated in two different ways: systemic and local. Among systemic application methods are major otohemotherapy, minor otohemotherapy, and rectal insufflation, while local application methods are low-pressure ozone application, transcutaneous ozone irrigation, subcutaneous and intracutaneous ozone application. It is a cost-effective and simple method to use; however, experience is needed in the application of the technique and management of the adverse effects.