Nogo-A is a cell surface protein of oligodendrocytes, myelin, and neurons which exerts potent inhibitory effects on growing neurites in the mammalian CNS. Its physiological role seems that of a controller of CNS plasticity and stabilizer of the complex CNS wiring. After injury, Nogo-A restricts fiber sprouting and regrowth and limits plastic rearrangements of connections. Nogo-A-neutralizing antibodies or receptor decoys applied intrathecally to spinal cord-injured rodents or monkeys enhanced regenerative fiber growth of different spinal tracts and led to a higher level of functional recovery. Clinical anti-Nogo-A antibodies have been produced and were shown to be well tolerated after intrathecal as well as intravenous administration in animals and humans. Phase II proof of concept trials in acute and chronic spinal cord-injured patients are currently ongoing. First promising exploratory results are being published.