Infection of a susceptible host with the blood fluke Schistosoma mansoni results in the formation of periovular granulomas and subsequent fibrosis in the target organs. Granulomogenesis and fibrogenesis are mediated by immunological events which require cell-cell and cell-matrix interactions. In this review, the role of adhesion and co-stimulatory molecules in the genesis of the schistosomal pathology (granulomogenesis and fibrogenesis) is outlined. These molecules provide essential immunological interactions not only for the initiation of granuloma formation but also for the maintenance and modulation of the schistosomal granuloma during chronic infection. Furthermore, the role of secreted soluble adhesion molecules in the different clinical forms and in the modulation of the schistosomal granuloma is discussed. Recent new insights into the role of adhesion molecules for the induction of pathology by other developmental stages of the parasite (other than eggs) will be presented.