The plasma membrane of cells contains a variety of lipid and protein molecules that are often segregated and heterogeneously distributed in microdomains. Lipid rafts represent a generalized concept of membrane microdomains that are enriched in cholesterol and sphingolipids and, characteristically, resistant to cold detergent extraction. Lipid rafts have recently received considerable attention because they are thought to be involved in many cellular functions, in particular, signal transduction for extracellular stimuli. Many of these functions are also intimately related to the processes involved in neural development, including neurotrophic factor signaling and synaptic plasticity. Recent studies from our lab and others have indicated an important role for lipid rafts in axonal growth and guidance. Specifically, our data show that lipid rafts on the plasma membrane provide platforms for spatial and temporal control of guidance signaling by extracellular cues. In addition, lipid rafts may also function in other aspects of axonal growth and guidance, including spatial and temporal regulation of adhesion, cytoskeletal dynamics, and growth cone motility. Further elucidating how membrane rafts are involved in guided axonal growth would provide important insights into the intricate signaling mechanisms underlying neuronal wiring, which is fundamental for normal brain development and functional recovery after injury and diseases.