Cell polarization and the establishment of functionally specialized domains play a pivotal role in many cellular processes such as vectorial transport of molecules, cell division and differentiation, directional movement of the cells in a chemotactic gradient and activation of the immune response. Cell polarization is a complex phenomenon, in which the interplay among cell cytoskeletal components, extra- and intracellular signals and organelle and membrane reorganization is crucial to achieve a correct cell shape change. The intracellular machinery needed for cell polarization has been elucidated in several well-established models, including yeast, epithelial, neuronal and germ-line cells. Cells of the immune system also polarize in response to extracellular cues, but many of the intracellular signals that control cell polarization and the role of genes with a well-defined function in other polarization processes are still unknown. In this review, recent advances in the study of leukocyte polarization are examined highlighting the similarities and differences with other models of cell polarization. The extracellular signals which direct cell polarization, the signal transduction pathways involved as well as the role of cell polarization in the development of the immune response are discussed.