Immune mediated inflammatory diseases (IMIDs) are life long conditions that cause substantial morbidity and disability. Though increasingly common and intensely studied, the cellular and molecular mechanisms underlying their pathogenesis are still unclear. Despite this incomplete knowledge, it is becoming increasingly evident that IMIDs evolve over time, not only from a clinical perspective but also a pathophysiological one. Evidence is accumulating that the events responsible for inflammation and damage in the target organs are not necessarily the same during the evolution of the IMID, and that the immune response evolves in parallel with the clinical manifestations. This has crucial implications for therapy because immunomodulatory interventions aimed at early pathogenic events may no longer be effective when these events have changed due to a different composition of the immune response. Therefore, it is crucial to better understand why and how the IMID associated immune abnormalities evolve over time, so that time-dependent therapies may be rationally implemented for an improved clinical outcome.