Parasitic weeds pose severe constraint on major agricultural crops. Varying levels of resistance have been identified and exploited in the breeding programmes of several crops. However, the level of protection achieved to date is either incomplete or ephemeral. Resistance is mainly determined by the coexistence of several mechanisms controlled by multigenic and quantitative systems. Efficient control of the parasite requires a better understanding of the interaction and their associated resistance mechanisms at the histological, genetic and molecular levels. Application of postgenomic technologies and the use of model plants should improve the understanding of the plant-parasitic plant interaction and drive not only breeding programmes through either marker-assisted selection (MAS) or transgenesis but also the development of alternative methods to control the parasite. This review presents the current approaches targeting the characterization of resistance mechanisms and explores their potentiality to control parasitic plants.