Barrier cells are a newly defined group of activated fibroblastic cells that are deployed as diverse barriers in the splenic pulp. The central capacity of the spleen, namely clearance of the blood, is normally modest but when stressed, for example by infectious disease, imperfect blood cells or the administration of interleukin 1, the clearance capacities of the spleen expand. The normally scarce barrier cells rapidly and greatly increase in number in splenic stress. By augmenting the splenic filtration beds, regulating blood flow, enveloping white pulp and enclosing hematopoietic colonies, they appear to be important in the spleen's increased capacities in clearance, phagocytosis, immunological reactivity and hematopoiesis. This review focuses on their role in the spleen, but barrier cells may appear throughout the body in response to needs for walling off and cellular induction.