Orobanchaceae-broomrapes-are a family of parasitic plants that represent an ecological and agronomic challenge because some of them cause significant damage to many monocots or dicots. Weedy broomrapes infest different crops in the Mediterranean basin, leading to substantial yield losses. Besides, they quickly adapt to new host plants, so that new crops are more and more under threat. Control methods are lacking because as plant parasites they cannot be considered as a common weed in agriculture. It is therefore important to characterize the main drivers of their regulation to identify sustainable management strategies.We reviewed all the possible interactions of Orobanchaceae species with surrounding organisms in an agricultural landscape, with a focus on the Orobanche and Phelipanche genera. Our main findings are that (1) broomrapes successfully co-evolve with their host through tight interactions ranging from the molecular to the tissue level, resulting in a unique strategy in their interactions with their host; (2) broomrapes have to face natural regulatory mechanisms such as host plant defenses, allelopathic interferences, and pest attacks from both the rhizosphere and phyllosphere; (3) alternative methods combining these natural mechanisms with existing conventional methods should be used to control broomrape. Conventional methods have shown limited results with parasitic weeds. By considering their life cycle and biotic and abiotic environment, management methods will target their weak point(s). Combining different control methods needs to be considered in an integrated weed management system. Furthermore, future studies on biocontrol will bring out new products to be used in addition to cultural techniques. Modeling approaches would help predict the evolution of broomrape-infested plots and the available potential management strategies.