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The development of endophyte inoculants for agricultural crops has been bedevilled by the twin problems of a lack of reliability and consistency, with a consequent lack of belief among end users in the efficacy of such treatments. We have developed a successful research pipeline for the production of a reliable, consistent and environmentally targeted fungal endophyte seed-delivered inoculant for barley cultivars. Our approach was developed de novo from an initial concept to source candidate endophyte inoculants from a wild relative of barley, Hordeum murinum (wall barley). A careful screening and selection procedure and extensive controlled environment testing of fungal endophyte strains, followed by multi-year field trials has resulted in the validation of an endophyte consortium suitable for barley crops grown on relatively dry sites. Our approach can be adapted for any crop or environment, provided that the set of first principles we have developed is followed. Here, we report how we developed the successful pipeline for the production of an economically viable fungal endophyte inoculant for barley cultivars., Competing Interests: The authors declare no conflict of interest.