The neutrophil has developed into one of the most efficient vertebrate motile cells. It migrates through tissues, where it encounters multiple chemoattractant signals with complex spatial and temporal characteristics. The directional movement of the neutrophil is signaled by the binding of chemoattractants and chemokines to G-protein-coupled receptors expressed on the plasma membrane. The signals from the ligand-bound receptors are transmitted along signaling pathways and initiate various cell responses, such as motility, superoxide production, and secretion. The signaling of the motility responses finds its climax in the polymerization of F-actin, which results in lamella formation and overall rearrangement of the cellular cytoskeleton and cell crawling. Also, during motility, adhesion receptors attach to and detach from their ligands and provide the necessary traction for crawling. These events are highly synchronized and allow the cell to orient in shallow chemoattractant gradients even when more than one chemoattractants are present. Due to the complexity of the motility responses, the signaling of their regulation is still not well understood. Recent advances in the understanding of the mechanism of F-actin polymerization have shown that the small GTPasess Cdc42, Rac2, and RhoA, play a critical role in motility. The bound integrin receptors may also contribute to the signaling of motility via tyrosine kinase phosphorylation of guanine nucleotide exchange factors and other regulatory proteins. In this review, we discuss the signaling of neutrophil motility in relation to the response of the cell to chemoattractant activation.