All stages in lymphocyte life and activation are associated with profound changes in cell morphology that depend on a functional tubulin and actomyosin cytoskeleton. Lymphocytes migrate through blood and lymph vessels, transgress vessel walls and extracellular matrix spaces, home into lymphoid organs, interact with antigen-presenting cells (APCs), and adhere to target cells. During lymphocyte maturation, developing T and B cell precursors are in continuous contact with stromal cells of the thymic or bone marrow microenvironments, and these physical contacts are crucial prerequisites for differentiation and selection. Since many signaling molecules are associated with cytoskeletal scaffolds, the cytoskeletal structure and scaffold geometries can directly regulate the molecular dynamics of signaling and biochemical responses. This minireview examines the emerging role of the actin cytoskeleton as an integral component of lymphocyte activation.