Simple SummaryThe association between hypoxia, cancer aggressiveness and decreased therapeutic response is well-established. With a significant body of evidence suggesting that tumor hypoxia is a poor prognostic indicator, it is important to identify and quantify the presence and magnitude of hypoxia within the tumor microenvironment. In this review, we aim to summarize the major molecular pathways associated with tumor hypoxia as well as the currently available evidence regarding the use of positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques for imaging hypoxia within the context of cancer. We also aim to propose future directions and discuss the challenges needed to be overcome in order to advance research in this field.AbstractMolecular and functional imaging have critical roles in cancer care. Existing evidence suggests that noninvasive detection of hypoxia within a particular type of cancer can provide new information regarding the relationship between hypoxia, cancer aggressiveness and altered therapeutic responses. Following the identification of hypoxia inducible factor (HIF), significant progress in understanding the regulation of hypoxia-induced genes has been made. These advances have provided the ability to therapeutically target HIF and tumor-associated hypoxia. Therefore, by utilizing the molecular basis of hypoxia, hypoxia-based theranostic strategies are in the process of being developed which will further personalize care for cancer patients. The aim of this review is to provide an overview of the significance of tumor hypoxia and its relevance in cancer management as well as to lay out the role of imaging in detecting hypoxia within the context of cancer.