Throughout biology, the pursuit of genotype-phenotype relationships has provided foundational knowledge upon which new concepts and hypotheses are built. Genetic perturbation, whether occurring naturally or in experimental settings, is the mainstay of mechanistic dissection in biological systems. The unbiased discovery of causal genetic lesions via forward genetics in patients who have a rare disease elucidates a particularly impactful set of genotype-phenotype relationships. Here, we review the field of genetic errors of immunity, often termed inborn errors of immunity (IEIs), in a framework aimed at highlighting the powerful real-world immunology insights provided collectively and individually by these (approximately) 500 disorders. By conceptualizing essential immune functions in a model of the adaptive arsenal of rapid defenses, we organize IEIs based on immune circuits in which sensors, relays, and executioners cooperate to carry out pathogen clearance functions in an effective yet regulated manner. We review and discuss findings from IEIs that not only reinforce known immunology concepts but also offer surprising phenotypes, prompting an opportunity to refine our understanding of immune system function.