Patients suffering from multiple organ dysfunction syndrome (MODS) comprise a heterogeneous population, which complicates research in its pathogenesis. Elucidation of the mechanisms involved in the development of MODS will ultimately necessitate the collection of tissue samples and the performance of invasive procedures. These requirements greatly reduce the possibilities for research in human subjects. Therefore, an animal model for MODS is a necessary and valuable tool. In the mid 1980s, the zymosan-induced generalized inflammation (ZIGI) model was introduced. Intraperitoneal injection of zymosan in mice or rats leads, in the course of 1 to 2 weeks, to increasing organ damage and dysfunction. The ZIGI model has been recognized as the one that best resembles human MODS and it has been used widely to study systemic inflammation in relation to organ failure. This review describes the ZIGI model and gives an overview of the results obtained.