Dysfunction of surviving axons which traverse the site of spinal cord injury (SCI) appears to contribute to posttraumatic neurological deficits, though the underlying mechanisms remain unclear. Although demyelination of injured but surviving axons following trauma appear to be a major contributor of axonal conduction deficits, altered activity of ion channels may also play an important role. It has been theorized that exposure of K+ channels as a result of demyelination would result in a reduced safety factor of action potential propagation across the demyelinated region of the axon. This theory and electrophysiological studies using K+ channel blockers on animal nerve preparations prompted the investigation of 4-aminopyridine (4-AP), a blocker of rapidly activating voltage-gated K+ channels, as a therapeutic agent in both multiple sclerosis and spinal cord injured patients. Several preliminary clinical trials have already demonstrated therapeutic benefit of 4-AP in both multiple sclerosis and spinal cord injured patients. In this review, we shall give a comprehensive summary of the mechanisms of axonal dysfunction following SCI and how axonal dysfunction may have resulted due to specific pathological changes following trauma including the ultrastructural and molecular changes that occur to myelinated axons. The pathology of spinal cord injury is very complex and many different mechanisms may contribute to axonal conduction deficits and the associated sensory and motor loss.