Introduction. The top 10 causes of death around the world are usually ranked with heart diseases, cancers, drugs/medication/iatrogenic chemicals, strokes etc. These are totally detectable, predictable, avoidable, preventable because it is classified as non-communicable diseases. Acute diseases are denoted by acute inflammation which has intensive cell-cell communications, resulting intensive repair rebuilding rehabilitation and it is life extending. Often it is self defensive and we over come it. The real culprit for chronic diseases is chronic inflammations, denoted by constant and silent, undetectable and insensible lost of cell-cell signaling, basement membrane disease, tight junction destructions, mitochondrial dysfunctions, mismatched metabolism, nutritional losses, mineral depletion, hormonal imbalances, opportunistic antigenicity wasting away the helpful immunity, leading to immune senescence and stem cell depletions eventually leading to chronic degeneration and devastating incapacitated regeneration ability. Often it is self destructive and we usually succumb to it. Mitochondrial decay & incapacitation of oxygenation and aerobic respiration failure leading to chronic anaerobic conditions breeding many chronic diseases. Ozone therapy is one of the best method to reverse chronic diseases. Its hormetic response curve of 10 to 80 gamma units typically reveals the secret of ozone healing hormesis. The low dose concept is to be respected all time. And with in safety limits we can practice low & escalating dosage, with increasing in volume of blood exposure to ozone, to evolve from minor AHT to major AHT, all the way into continuous auto-hemotherapy via extra-corporeal blood circuits with the proper method. Its action on mitochondrial health and its regenerative power is well known and documented. Method: 1. Ozone properties and therapeutic applications and methods of extracorporeal circuits 2. EBOO / AQUAPHERESIS set up and therapy method 3. Safeties and precautions, limitations and patient selections 4. Selections of machines and GED gas exchange devices 5. Therapeutic steps for patient, and adjuvant photonic therapy 6. Post therapeutic monitoring and documentations 7. Clinical results of various cases treated with EBOO and AQUAPHERESIS Results. Definition of extra corporeal circulations method would be discussed. Original EBOO therapy method and scientific studies would be reviewed. A modified economical method of EBOO would be illustrated. A further improvised AQUAPHERESIS method of continuous blood ozonation / oxygenations would be illustrated and discussed. To ensure safety and long term success, selection of machines, materials, circuits, disposables, disposal of dialysates and ozone residue, all the way to selections of dialyzer and GED gas exchange devices would be discussed. Dangers of wrong machines and wrong GED/Dialyzers with related precautions to be considered during EBOO and AQUAPHERESIS would be discussed. A few case study would be illustrated and discussed. Conclusions. Ozone is a wonderful new well known medical drug. Its benefits is vast and economically easily available. Within the safety limits we can extend the ozonation and oxygenation of blood to a much longer, larger therapeutic window via the extra corporeal circuit method. Both EBOO and AQUAPHERESIS are additional interesting method to deliver ozone therapy to patient reaping also the benefits of plasma apheresis in AQUAPHERESIS method. With correct knowledge and higher standard of machines and disposables, these methods are safe and effective to be applied to patient and it deliver significant result clinically. Further studies are encouraged and worth explored.