Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is a protein encoded by theNOD2gene and plays an important role in the immune system. NOD2 is an intracellular pattern recognition receptor (PRR) responsible for the recognition of pathogens as well as the activation of many biochemical processes within cells of the host immune system. Mutations of theNOD2gene can significantly impact the host's immune response against a variety of pathogens. In addition to immunodeficiency, mutations of theNOD2gene have also been linked with several atopic diseases and autoimmune conditions such as rheumatoid arthritis and Crohn's disease (CD). There is also a distinct set of autoinflammatory conditions that are now classified as NOD2-associated autoinflammatory diseases (NAID). We present a case of a 63-year-old female with common variable immunodeficiency, eosinophilic asthma, and rheumatoid arthritis who was found to have aNOD2mutation on genetic testing. As genetic testing continues to gain popularity, several disease states that were previously thought to be unrelated are now being recognized as originating from a common genetic defect.