The spleen can exert different functions: hematopoiesis, immune response, blood filtration, and blood storage. Presence and importance of each function vary among different species and, within a single species, vary during ontogeny. During the course of evolution, loss of hematopoietic functions was accompanied by increased specialization of other functions. Increase in the complexity of immunological features can be seen in the passage from scattered lymphocytes to segregation of the white pulp, organization of T- and B-lymphocyte regions and, finally, appearance of germinal centers. The red pulp remained essentially the same in all nonmammalian vertebrates, with a microarchitecture that concentrates blood and allows its filtration. In our view, this high splenic hematocrit was eventually co-opted in teleosts and mammals to develop a new function: the storage of red blood cells. Finally, mammalian species evolved different features of the red pulp, increasing the specialization of the filtration function (pulp sinuses) and/or storing function (muscularization)