This chapter focuses on the adhesion, chemoattraction, and migration of leukocytes, particularly T cells that are associated with autoimmune responses. The molecules that facilitate cell migration, such as adhesion molecules and chemoattractant receptors, also represent highly attractive targets for therapeutic intervention. Moreover, chemokine receptors and adhesion molecules have proved to be excellent markers for distinguishing functional subsets of T and B cells, since certain subsets need to be placed in the appropriate place to perform their immunologic roles. It is noted that, under resting conditions, lymphocyte migration is highly rationalized, with the existence of lymphoid versus non-lymphoid tissue migration streams, and tissue-specific migration pathways through the skin and gut. Furthermore, adhesion molecules and chemoattractant receptors are particularly promising targets for the development of new therapies to treat autoimmune diseases. Numerous antibodies, recombinant soluble adhesion molecules, receptor blocking mutant chemokines, and small molecules are being tested for clinical application in multiple sclerosis, inflammatory bowel disease, arthritis, and psoriasis.