Multidrug resistance (MDR) continues to be a major challenge to effective chemotherapeutic interventionsagainst cancer. Various types of cancers have been observed to exhibit this phenomenon, a strategy that involvescellular and non cellular mechanisms employed by cancer cells to survive the cytotoxic actions of variousstructurally and functionally unrelated drugs. The present article is a brief review of the fundamental mechanismsunderlying the phenomenon of MDR in cancer cells and some novel approaches addressed at its inhibition,circumvention or reversal. The emergence of natural products as potential anti-MDR molecules is of particularsignificance. Since many of these are essential components of the human diet, they are expected to possess fewerside effects and may possibly represent a new generation of MDR modulators.