The AP2/ERF (APETALA2/ethylene response factor) family of transcription factors plays a crucial role in plant disease resistance. This review highlights recent advances in understanding the functions of AP2/ERFs in defense responses against microbial pathogens. AP2/ERFs are involved in plant disease resistance by acting downstream of mitogen-activated protein kinase (MAPK) cascades and regulating genes associated with hormonal signaling pathways, secondary metabolite biosynthesis, and physical barrier formation. They can act as transcriptional activators or repressors, integrating hormonal signaling to modulate plant defense responses. Additionally, AP2/ERFs are key regulators in the crosstalk between different signaling pathways, such as those involving salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). The review also discusses the role of AP2/ERFs in manipulating the biosynthesis of secondary metabolites and physical barriers, such as lignin and cutin, to enhance plant resistance. The identification and characterization of novel AP2/ERF family members and their underlying mechanisms will contribute to the development of strategies for improving plant disease resistance.The AP2/ERF (APETALA2/ethylene response factor) family of transcription factors plays a crucial role in plant disease resistance. This review highlights recent advances in understanding the functions of AP2/ERFs in defense responses against microbial pathogens. AP2/ERFs are involved in plant disease resistance by acting downstream of mitogen-activated protein kinase (MAPK) cascades and regulating genes associated with hormonal signaling pathways, secondary metabolite biosynthesis, and physical barrier formation. They can act as transcriptional activators or repressors, integrating hormonal signaling to modulate plant defense responses. Additionally, AP2/ERFs are key regulators in the crosstalk between different signaling pathways, such as those involving salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). The review also discusses the role of AP2/ERFs in manipulating the biosynthesis of secondary metabolites and physical barriers, such as lignin and cutin, to enhance plant resistance. The identification and characterization of novel AP2/ERF family members and their underlying mechanisms will contribute to the development of strategies for improving plant disease resistance.