In contrast to normal tissues, tumors thrive in hypoxic environments. This appears to be because they can metastasize and secrete angiopoietins for enhancing neoangiogenesis and further tumor spread. Thus, during chronic ischemia, normal tissues tend to die, while neoplasms tend to grow. During the past two decades, it has been shown in arteriopathic patients that ozonated autohemotherapy is therapeutically useful because it increases oxygen delivery in hypoxic tissues, leading to normoxia. Although several oxygenation approaches have been tested, none is able to restore normoxia permanently in patients with cancer. We postulate that a prolonged cycle of ozonated autohemotherapy may correct tumor hypoxia, lead to less aggressive tumor behavior, and represent a valid adjuvant during or after chemo- or radiotherapy. Moreover, it may re-equilibrate the chronic oxidative stress and reduce fatigue.