From the early days of radiotherapy in the middle of the 20th century, the empirical knowledge has increased tremendously with time due to high rate of growth in technical innovations. The technical development of radiotherapy is, however, independent of the tumor type but restricted to the individual radiosensitivity of patients depending on their susceptibility that is genetically determined. The mechanisms dictating radio- and chemoresistance are multifactorial; therefore the combination of radio- and chemotherapy does not necessarily always meet the clinical requirements. There is a vast amount of literature concerning the modulation of radioresistance or drug resistance. Surprisingly, a number of radiosensitizers also increase the sensitivity of tumor cells to cytostatic drugs. Ayurvedic medicine or Ayurveda, the ancient health care system native to the Indian subcontinent followed for several centuries traditionally and sacredly comprises of several herbal plants that are proven to be efficient in anticancer therapy scientifically. Some of these ayurvedic herbal plants are known to exhibit their antitumor property indirectly by enhancing the tumoricidal effects of chemotherapy and radiotherapy. Their phytoconstituents protect normal cells from therapy-induced damage, and increase systemic bioavailability of chemotherapeutic agents. In this chapter, the various molecular mechanisms and modulators involved in radio- and chemoresistance are mentioned. Of special interest, natural products as referred in Ayurveda, especially, curcumin (from Curcuma longa) and withanolide A (from Withania somnifera) are described for their role in the modulation of radio- and chemoresistance.