Plants rely on germline-encoded, innate immune receptors to sense pathogens and initiate the defense response. The exponential increase in quality and quantity of genomes, RNA-seq datasets, and protein structures has underscored the incredible diversity of plant immunity. Arabidopsis continues to serve as a valuable model and the theoretical foundation of our understanding of wild plant diversity of immune receptors, but expansion of study into agricultural crops has also revealed distinct evolutionary trajectories and challenges. Here, we provide the classical context for study of both intracellular nucleotide-binding, leucine-rich repeat receptors (NLRs) and surface-localized pattern recognition receptors (PRRs) at the levels of the DNA sequences, transcriptional regulation, and protein structures. We then examine how recent technology has shaped our understanding of immune receptor evolution and informed our ability to efficiently engineer resistance. We summarize current literature and provide an outlook on how researchers take inspiration from natural diversity in bioengineering efforts for disease resistance in crops. This work has been submitted to The Plant Cell as an invited review for the special focus issue “Translational Research from Arabidopsis to Crop Plants and Beyond”.