Monoclonal proteins (paraproteins) may be detected in the sera in approximately 1% of the general population and are frequently associated with peripheral neuropathy. Paraproteinemic neuropathy (PPN) is most commonly associated with monoclonal gammopathy of undetermined significance, and may also occur in the context of multiple myeloma, amyloidosis, cryoglobulinemia, and other hematologic malignant and nonmalignant conditions. Possible malignant conversion of underlying benign monoclonal gammopathy should be closely monitored, and risk factors include progression of neuropathy and rising titers of monoclonal protein. PPN is frequently associated with autoantibodies targeting peripheral nerve antigens, including anti-MAG and anti-GM1 antibodies. Therapy is mostly based on the treatment of the underlying hematologic disorder. Risks and benefits should be carefully evaluated as treatment may be associated with considerable morbidity. Rituximab may be helpful in treatment of IgM-PPN, and paraproteinemic multifocal motor neuropathy usually responds to IVIG. Plasmapheresis is more effective with IgG/IgA paraproteinemic neuropathies. At this time it is not clear whether mere presence of neuropathy warrants more aggressive treatment of otherwise quiescent hematologic malignances (e.g. smoldering myeloma).