In this issue of Immunology and Allergy Clinics, guest editors Drs. Cullen M. Dutmer and Jessica Galant-Swafford bring their considerable expertise to the topic of Immune Deficiency. This issue is designed to enhance readers’ understanding of molecular diagnostic approaches for inborn errors of immunity and build a framework for interrogating gene sequencing results; help clinicians recognize the prevalence and importance of non-infectious complications of inborn errors of immunity, consider therapeutic interventions that are tailored to the molecular diagnosis, and learn to identify approaches to hasten time to diagnosis of inborn errors of immunity; and review the role of immunoglobulin therapy in managing disease and revisit how vaccinations can aid in probing humoral immunity integrity.