Immune-mediated inflammatory diseases (IMID) represent a diverse group of chronic conditions that share common pathways. Although the etiology of IMID has yet to be identified, it is well known that both genetic and environmental factors play an important role in the development of these disorders. Genome-wide association (GWA) studies and GW nonsynonymous single-nucleotide polymorphism (nsSNP) scans have recently led to identification of genes commonly found in several different IMID as well as those that are disease-specific. Current epidemiological, clinical, and experimental evidence has also confirmed an association between IMID and a large number of seemingly unrelated environmental factors, which include smoking, diet, drugs, geographical and social status, stress, and microbial agents. Data supporting the involvement of each of these factors in predisposing to, triggering, or modulating the course or outcome of IMID vary from strong to tenuous. The notion of shared genetic pathways creates new and powerful approaches for discovering the full spectrum and potential of susceptible genes in these potentially disabling chronic conditions. Insights relating to a specific immune pathway could provide targets for therapeutic interventions.