Multidrug resistance (MDR) is a kind of resistance of cancer cells to multiple classes of chemotherapic drugs that can be structurally and mechanistically unrelated. Classical MDR regards altered membrane transport that results in lower cell concentrations of cytotoxic drug and is related to the over expression of a variety of proteins that act as ATP-dependent extrusion pumps. P-glycoprotein is the most important and widely studied member of the family that belongs to the ABC superfamily of transporters. It is apparent that, besides its role in cancer cell resistance, this protein has multiple physiological functions as well, since it is expressed also in many important non-tumoural tissues and is largely present in prokaryotic organisms. Several novel MDR reversing agents (also known as chemosensitisers) are currently undergoing clinical evaluation for the treatment of resistant tumours. In this work, the effects of natural compounds on P-glycoprotein and anticancer drug efflux transporters are summarized.