One of the most difficult barriers encountered when treating the majority of solid tumours is attributed to the scattered microregions within the tumour characterized by the lack of oxygen. This is known as tumour hypoxia. The lack of oxygen supply results in hypoxic microregions scattered throughout the tumour relative to normal tissue. The hypoxic environments within tumours create several cancer treatment barriers. Most notably, all hypoxic cells are resistant to ionizing radiation (IR). The mechanism by which radiation is able to eradicate tumour cells by damaging DNA, resulting in apoptosis and cell death, occurs through the production of reactive oxygen species (ROS). However, due to the limited oxygen availability within hypoxic tumour microenvironments, this impedes the efficacy of radiotherapy. Furthermore, normal tissues are unable to withstand increased doses of radiation that compensate for tumour hypoxia. Methods targeting tumour hypoxia through radiosensitizing hypoxic cells include hyperbaric oxygen, hypoxic cell radiosensitizers, hypoxic cytotoxins, and tumour metabolism. As research continues to elucidate the relationship between tumour hypoxia and radiotherapy, novel approaches have been developed.