The fascinating biology of Striga parasitism is manifest through a series of signal exchanges between the parasite and its host. As an obligate root hemi-parasite, Striga development is cued to exudates and solutes of host roots but with negative ramifications on host plant health. Striga control in crops, via a variety of biotechnological approaches, needs to be based on increased understanding of this intricate biology. Maize has become the major cereal crop of Africa. However, this New World transplant has shown a paucity of Striga resistance characters relative to native sorghum. In this paper, we review growing evidence for maize genetic defenses against early pre-emergent phases of the Striga life cycle, when the tolls of parasitism are first manifest. Resistance characters first described in maize wild relatives have now been captured in Zea mays. The possible stacking of new and complementary sources of resistance in improved maize varieties targeted for Striga prone areas is discussed. An integrated approach combining genetic with other control measures is advocated with a more realistic view of the resource challenges prevalent in African agriculture.