Near-infrared spectroscopy measures of haemoglobin oxygen saturation are often used as an indicator of sufficient oxygen delivery to assess injury susceptibility and tissue damage. They have also often been used as a surrogate measure of oxygen metabolism. Unfortunately, these measures have generally failed to provide robust indicators of injury and metabolism. In this paper, we first review when haemoglobin oxygen saturation does work as a robust indicator, and then detail when and why it fails for assessing brain injury and breast cancer. Finally, we discuss the solution to obtain more robust measures of tissue injury and cancer by combining oxygen saturation measurements with measures of blood flow and volume to more accurately estimate oxygen metabolism.