Chronic inflammation is the result a persistent increase in the expression of several proinflammatory pathways with impaired inflammatory resolution. Ectopic lymphoid organs (ELOs), untypical lymphoid annexes, emerge during chronic inflammation and contribute to the physiopathology of chronic inflammatory disorders. This review discusses the pathophysiological role of ELOs in the progression of immune-mediated inflammatory diseases (IMIDs), including multiple sclerosis (MS), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), atherosclerosis, and Sjögren syndrome (SSj). The molecular pathways underlying the emergence of ELOs are of interest for the development of novel pharmacological approaches for the management of chronic inflammatory diseases.