The major drawback of cancer chemotherapy is the development of multidrug resistant (MDR) tumor cells, which are cross-resistant to a broad range of structurally and functionally unrelated agents, making difficult the treatment of such tumors. Treatment of MDR tumors refractory to conventional chemotherapy is presently the foremost concern of oncologists because these tumors need additional drugs to revert the MDR phenotype, which in most cases are highly toxic to the whole organism. In the last decade a number of authors studied the response of MDR cells to non-ionizing radiation, applied either alone or in combination with photosensitizing agents (photodynamic therapy- PDT), and although the results are still inconclusive, they raised the possibility of treating MDR tumors by PDT. This review examines the growing literature concerning the response of MDR cells to non-ionizing radiation, underscoring what has been done and what needs to be elucidated in order to proclaim phototherapy as a new insight for the treatment of MDR tumors.