Demyelination of axons within the spinal cord represents a significant component of the pathology of contusive and compressive spinal cord injury (SCI) and the associated conduction deficits most probably contribute to the paralysis and sensory loss experienced by SCI patients. 4-Aminopyridine (4-AP) is a potassium (K+) channel blocking agent that has been shown capable of restoring conduction across demyelinated internodes in neurons of the spinal cord. Recent clinical trials of 4-AP provide evidence that limited and transient neurological gain may be derived by some SCI patients with longstanding injury. The present review traces the historical development of 4-AP, describes the mechanism of action and rationale for use in SCI, and provides an overview of the clinical trials conducted to date. The early trials give rise to optimism that pharmaceutical management of conduction deficits may have a role to play in restoring neurological function in some patients with SCI.