Abstract Striga spp. is a major threat to cereal and legume production, putting the food security and economy of smallholder farmers in sub-Saharan Africa at severe risk. This is manifested in the fact that Striga spp. infestation can result in up to 90% loss of both cereal and legume production. A consensus exists that there is yet no single measure to efficiently control Striga spp. This is mainly because of the limited fundamental knowledge of the genetics and ecology of Striga spp. and its interaction with its hosts and host root-associated microorganisms, including plant growth-promoting rhizobacteria (PGPR). Since Striga spp. is a root parasite, it is speculated that PGPR play a key role in controlling the emergence and development of Striga spp. At the same time, PGPR may exhibit beneficial effects on growth promotion of the host to strengthen its tolerance against Striga spp. attacks, while on the other hand, it may also induce, similar to biocontrol agents, direct suicidal effects on Striga spp. Such hypothesized associations between Striga spp., crops (e.g., cereals such as sorghum and maize), and PGPR remain largely unknown, and the central question remains if PGPR play an important role in the Striga -crop pathosystem. This knowledge gap is the central impetus of this review. It will elaborate the complex and fascinating tripartite ecological system of cereals, Striga spp. and root-associated microorgamisms. In a first step, the review will provide a comprehensive summary of the pairwise interactions between Striga spp. and cereals, cereals and PGPR, as well as Striga spp. and PGPR. This summary will then merge into the discussion about the yet limited knowledge of the tripartite interaction between cereals, Striga spp., and PGPR. This specifically includes the exploration of recent discoveries related to population genetics and the life cycle of Striga spp, host (cereal) defense responses to and mechanisms of Striga spp. infestation, as well as the inhibitory and stimulatory role of PGPR on Striga spp. seed germination. In a concluding section, remaining research gaps are identified and necessary research perspectives are provided to direct prospective research toward further understanding the relationship between the three biological components paving the avenue to develop biological and environmentally friendly measures to fight off the everlasting threat of Striga spp.