Agricultural production in arid and semiarid regions relies mainly on irrigation. Due to the scarcity of water resources in these regions, the use of marginal water sources (saline water and treated effluent) for irrigation is on the rise. Marginal water can contain high concentrations of salts and toxic microelements. Long-term use of this water for irrigation can decrease fruit yield and increase the accumulation and concentration of toxic elements in the plant and fruit. The effects of grafting on the uptake and distribution of toxic microelements within the plant were determined in several experiments conducted in the field and in greenhouses. In general, grafting of melon plants onto Cucurbita rootstock increased their tolerance to salinity and to high concentrations of toxic elements. Moreover, the concentrations of toxic elements, such as B, Zn, Sr, Mn, Cu, Ti, Cr, Ni, Cd, and Na, were lower in the shoots and fruit of grafted vs. non-grafted plants. Quantitative calculations of the toxic elements' concentrations in the xylem-sap exudates and in plant shoot and root tissues revealed exclusion and retention of these elements by the pumpkin root system. Grafting appears to be potentially useful for increasing the tolerance of vegetable crops to toxic elements, and for preventing the entry of contaminants and saline elements into the human food supply. Therefore, grafting is suggested as a useful tool for successful vegetable growth under arid and semiarid conditions.