For functional genomics of inflammatory disorders and infection, rheumatic diseases offer unique features to analyse the transition from infection to chronic inflammation, autoimmunity and immunopathology, both systemic and tissue specific. The diseases are frequent and of considerable socio-economic impact. Well-defined cohorts of patients are available. The tissues and cells involved are readily accessible for molecular analysis. Both genetic predisposition and infection are involved in the aetiopathogenesis of rheumatic diseases. The number of susceptibility and severity genes has been estimated to be at least 30, but only few of them have been identified so far. There is an urgent need for developing new therapies adapted to genetic risk and based on a functional genetic and molecular understanding of chronic inflammation. It is evident that gene analysis in inflammatory rheumatic diseases will not only be beneficial for the large number of patients involved, but will also lead to a better understanding of other inflammatory disorders, thereby possibly leading to novel diagnostic and therapeutic strategies in this important group of disorders.