•How do long-lived trees respond effectively to fast-evolving pathogens?•Is there evidence for dynamic pathogen-specific recognition within tree defence genes?•We propose that tree defence uses a three-pronged genomic approach.•This involves gene numbers, genomic architecture, and lifetime mutation loads. Perennial plants need to cope with changing environments and pathogens over their lifespan. Infections are compartmentalised by localised physiological responses, and multiple apical meristems enable repair and regrowth, but genes are another crucial component in the perception and response to pathogens. In this opinion article we suggest that the mechanism for dynamic pathogen-specific recognition in long-lived plants could be explained by extending our current understanding of plant defence genes. We propose that, in addition to physiological responses, tree defence uses a three-pronged genomic approach involving: (i) gene numbers, (ii) genomic architecture, and (iii) mutation loads accumulated over long lifespans.