Plants have evolved intricate defense mechanisms to combat pathogens, deploying a distinct line of protection that involves the activation of genetic responses within their cells through specialized proteins encoded by a class of defense genes known as R genes. In this regard, numerous defense-related genes, such as nucleotide-binding site–leucine-rich repeat (NBS–LRR) genes, play pivotal roles. NBS-LRR proteins, equipped with an amino-terminal variable domain, a central nucleotide-binding site (NBS), and a carboxy-terminal leucine-rich repeats (LRR) domain, exhibit the remarkable ability to recognize pathogens either directly or indirectly. Once activated, these proteins initiate downstream signaling pathways, triggering a robust defense response in plants against various biotic stresses, including bacterial, fungal, viral, nematode, and insect attacks. Notably, the NBS domain serves as a critical hub, binding to and hydrolyzing ATP to facilitate signal transduction upon pathogen recognition. Equally significant, the LRRs possess exceptional adaptability as structural domains, primarily involved in facilitating protein–protein interactions. Furthermore, LRRs can evolve with diverse binding specificities, adding to the plant’s repertoire of defense strategies. Within this chapter, we delve into the comprehensive genomic analysis of the resistance (R) gene family in leguminous plants. Our objectives encompass a wide array of facets, including the precise identification and meticulous annotation of R genes, an exploration of their intricate structural organization, a comparative genomics perspective, an examination of their expression patterns when exposed to biotic stress conditions, and insights into their practical applications in breeding programs. By undertaking this multifaceted approach, we aspire to elevate our understanding of the R gene family’s dynamics within the legume realm. Ultimately, this knowledge holds the promise of contributing significantly to the development of disease-resistant leguminous varieties, thereby bolstering agricultural sustainability in the face of ever-evolving pathogenic challenges.