A number of in vitro and in vivo observations have implicated plasminogen in contributing to events associated with diverse physiological and pathophysiological processes. The development of gene knockout technology has led to the generation of plasminogen deficient mice. These mice survive to adulthood and are thus a valuable resource for directly assessing its role in these processes. As a result, fibrinolytic and nonfibrinolytic functions have been identified from studies in which these mice were challenged utilizing a number of models that mimic both normal biological and pathological events.