Ozone application that can be used by the physicians after publishing of the Ministry of Health Traditional and Complementary Medicine Regulations may have the most common area of use in musculoskeletal conditions. The mixture of gas includes 5% ozone and the rest is oxygen. It can be regarded as a vaccination due to its effect of triggering an acute oxidative stress. It is generally considered to have effects on natural anti-oxidant system, regulation of metabolic enzymes and hormones, immune system, and cell regeneration. There are limited publications on ozone therapy in medical literature; even if it has shown an increase in recent years. The effectiveness of ozone therapy depends on accurate application technique and dose decided by the physician. This paper is dealing with basic principles of using medical ozone therapy in painful musculoskeletal conditions.