Chronic idiopathic axonal polyneuropathy is a disorder of unknown etiology resulting in progressive weakness and sensory disturbances predominantly in the hands and feet. Nerve conduction studies and electromyography confirm axonal damage in the nerves of the upper and lower extremities. The pathology is symmetrical with a distal predilection. Patients usually do not respond to the classical treatment with steroids, intravenous immunoglobulin, plasmapheresis, or immunosuppressant drugs. We describe 2 cases of chronic idiopathic axonal polyneuropathy who received intravenous rituximab as a last resort because of the severity of their symptoms. Both patients showed dramatic improvement in their weakness, muscle atrophy, numbness, and paresthesias only few weeks after the induction dose. Their daily functional activities improved to self-independence.