While pressurized oxygen in tank form, as well as oxygen concentrators, are ubiquitous in civilian healthcare in developed countries for medical use, there are a number of settings where use of these oxygen delivery platforms is problematic. These settings include but are not limited to combat casualty care and healthcare provided in extreme rural environments in undeveloped countries. Furthermore, there are a number of settings where delivery of oxygen other than the pulmonary route to oxygenate tissues would be of value, including severe lung injury, airway obstruction, and others. This paper provides a brief overview of the previous and current attempts to utilize chemical oxygen production strategies to enhance systemic oxygenation. While promising, the routine use of chemically produced oxygen continues to pose significant engineering and physiologic challenges.