The chapter discusses the evolution and development of plant immune systems, highlighting the significant impact of plant diseases on human and environmental health. Over the past 100 years, plant breeders have identified Mendelian genetic loci conferring resistance to specific pathogens, which has been crucial for modern agriculture. The emergence of model plants for genetics and genomics research has provided rich resources for molecular biological exploration. These studies have led to the identification of extracellular and intracellular receptors that convert recognition of pathogen-encoded molecular patterns or virulence effectors into defense activation. These receptor systems and downstream responses define plant immune systems that have evolved over 500 million years. The chapter also reviews the historical context of plant disease research, noting that crop diseases have historically impacted societies and food security. Despite advancements in understanding plant-microbe interactions, crop diseases persist, and the use of agrichemicals remains prevalent. The development of molecular plant-microbe interaction (MPMI) as an emerging field in the 1970s and 1980s has been driven by the need to address these challenges. Key milestones in plant immunity research are highlighted, including the discovery of the gene-for-gene model, the identification of immune receptor genes, and the cloning of avirulence (Avr) genes. The chapter emphasizes the importance of model systems like *Arabidopsis thaliana* in advancing the field, particularly in the identification of immune receptors and their interactions with pathogen effectors. Recent advances in structural biology have provided insights into the mechanisms of NLR proteins, which are central to plant defense. The chapter discusses the role of NLR proteins in pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), and the involvement of helper NLRs in signaling pathways. It also explores the diversity of immune receptor pairs and the concept of integrated decoy domains, which allow plants to recognize and respond to a wide range of pathogen effectors. Finally, the chapter touches on the extraordinary diversity of prokaryotic virulence factors and eukaryotic microbial pathogens, emphasizing the importance of comprehensive pan-genome sequences and gene expression data in understanding and controlling plant diseases.The chapter discusses the evolution and development of plant immune systems, highlighting the significant impact of plant diseases on human and environmental health. Over the past 100 years, plant breeders have identified Mendelian genetic loci conferring resistance to specific pathogens, which has been crucial for modern agriculture. The emergence of model plants for genetics and genomics research has provided rich resources for molecular biological exploration. These studies have led to the identification of extracellular and intracellular receptors that convert recognition of pathogen-encoded molecular patterns or virulence effectors into defense activation. These receptor systems and downstream responses define plant immune systems that have evolved over 500 million years. The chapter also reviews the historical context of plant disease research, noting that crop diseases have historically impacted societies and food security. Despite advancements in understanding plant-microbe interactions, crop diseases persist, and the use of agrichemicals remains prevalent. The development of molecular plant-microbe interaction (MPMI) as an emerging field in the 1970s and 1980s has been driven by the need to address these challenges. Key milestones in plant immunity research are highlighted, including the discovery of the gene-for-gene model, the identification of immune receptor genes, and the cloning of avirulence (Avr) genes. The chapter emphasizes the importance of model systems like *Arabidopsis thaliana* in advancing the field, particularly in the identification of immune receptors and their interactions with pathogen effectors. Recent advances in structural biology have provided insights into the mechanisms of NLR proteins, which are central to plant defense. The chapter discusses the role of NLR proteins in pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), and the involvement of helper NLRs in signaling pathways. It also explores the diversity of immune receptor pairs and the concept of integrated decoy domains, which allow plants to recognize and respond to a wide range of pathogen effectors. Finally, the chapter touches on the extraordinary diversity of prokaryotic virulence factors and eukaryotic microbial pathogens, emphasizing the importance of comprehensive pan-genome sequences and gene expression data in understanding and controlling plant diseases.