Cell motility and chemotaxis can make important contributions to the metastatic cascade. Cell migration pathways in general play significant roles in a variety of physiological processes that can be "hijacked" by cancer cells. Both growth factors and chemokines provide important chemotactic signals in development and metastasis. Receptor activation, following binding of a growth factor or a chemokine, leads to dynamic morphological changes in the actin cytoskeleton network via a variety of distinct and interconnected pathways, resulting in translocation of the cell up a chemoattractant gradient. Such gradients may be produced by stromal cells in the local microenvironment, including macrophages and fibroblasts. A better understanding of the mechanisms of cell motility and cytoskeletal regulation may provide novel therapeutic strategies that would block metastatic progression, reducing dissemination of tumor cells and increasing patient survival.