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Cell guidance is a key mechanism of cell positioning in multicellular organism during development and in tissue regeneration in adulthood. Each cell is continuously exposed to multiple guidance signals including soluble growth factors and cytokines, cell surface ligands such as ephrins, semaphorins, cadherins and selectins and extracellular matrix components. These multiple guidance cues are resolved and integrated into coherent instructions for cell navigation. Guidance signals are integrated and resolved at the stage of ligand receptor binding, receptor spatial rearrangement and downstream phosphorylation cascade. Coreceptor engaged, localization to lipid microdomains, membrane thickness, and local intracellular phosphatase activity may switch between opposite cell response to the same guidance cue. Mechanisms of guidance signal processing will be discussed with the emphasis on ephrin/Eph signaling.