Members of the CD44 protein family are engaged in various physiological and pathological processes such as lymphocyte activation, lymphocyte homing, wound healing, delayed type hypersensitivity, apoptosis, tumor progression and limb development. Here we summarize observations which lead to a molecular understanding of the function of CD44 in some of these physiological processes. The most striking function for a CD44 variant protein is its presentation of growth factors to high affinity receptors on mesenchymal cells in the developing limb. Furthermore we summarize the experiments that allowed the identification of CD44 variant exon encoded sequences which account for differentiation-specific and inducible splice regulation.