Allelopathic activity of wheat (Triticum aestivum L.) has previously been associated with the production of phenolic acids and flavonoids (PAF), benzoxazinones (BXZs) and phenoxazinones (PXZs). The biosynthesis of BXZs is closely regulated during cereal growth, with accumulation highest in young tissues with variation associated with genotype and environmental conditions. This review is focused on BXZ metabolites and their impact on germination, seedling growth and physiological, biochemical, transcriptional and proteome traits of surrounding plants and weeds. The major pathways employed by plants for benzoxazinoid detoxification involve hydroxylation and glucosylation and polymerisation of intermediates in these pathways. Allelochemicals from various wheat genotypes have been shown to inhibit the growth of selected weed species, including Bromus japonicus, Chenopodium album, Portulaca oleracea, Avena fatua and Lolium rigidum. Wheat allelopathy is potentially exploited from the standpoint of crop mulches, incorporation of crop residues, tissue disruption, intercropping with allelopathic cultivars and application of aqueous wheat extracts. BXZs have been shown to suppress the growth and development of certain agricultural pests, including insects, fungal pathogens, and weeds. Many native plants, fungi and insect herbivores inherently possess varying tolerance levels towards BXZs. However, other BXZ- susceptible species are adversely impacted by elevated BXZ levels in crop plants. Thus, considerations for the selection and breeding of wheat genotypes possessing enhanced defensive ability via elevated BXZ contents are discussed. Here, these objectives are reconsidered with a focus on co-evolutionary aspects and their potential impacts on biodiversity in the agroecosystems under study. For future breeding efforts to be successful, it is important to take such potential adverse environmental impacts into account, in combination with an increased focus on enhancing beneficial allelopathic effects within agricultural systems.