| Summary: | <i>Cannabis</i> (<i>Cannabis sativa</i> L.) is one of the earliest cultivated crops, valued for producing a broad spectrum of compounds used in medicinal products and being a source of food and fibre. Despite the availability of its genome sequences, few studies explore the molecular mechanisms involved in pathogen defense, and the underlying biological pathways are poorly defined in places. Here, we provide an overview of <i>Cannabis</i> defence responses against common pathogens, such as <i>Golovinomyces</i> spp., <i>Fusarium</i> spp., <i>Botrytis cinerea</i> and <i>Pythium</i> spp. For each of these pathogens, after a summary of their characteristics and symptoms, we explore studies identifying genes involved in <i>Cannabis</i> resistance mechanisms. Many studies focus on the potential involvement of disease-resistance genes, while others refer to other plants however whose results may be of use for <i>Cannabis</i> research. Omics investigations allowing the identification of candidate defence genes are highlighted, and genome editing approaches to generate resistant <i>Cannabis</i> species based on CRISPR/Cas9 technology are discussed. According to the emerging results, a potential defence model including both immune and defence mechanisms in <i>Cannabis</i> plant–pathogen interactions is finally proposed. To our knowledge, this is the first review of the molecular mechanisms underlying pathogen resistance in <i>Cannabis</i>.
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