Peripheral nerve amyloidosis is the cardinal feature of familial amyloid polyneuropathy (FAP) but can also be seen in primary light chain (AL) amyloidosis and dialysis (beta 2-microglobulin) related amyloidosis. The generalized neuropathy seen in all forms of peripheral nerve amyloidosis is similar, characterized by a severe progressive mixed neuropathy with autonomic dysfunction. Pathologically, amyloid is found in the peripheral nervous system as amorphous, eosinophilic, extracellular deposits. FAP is most commonly associated with variant plasma transthyretin (TTR), although it has also been described in association with mutant apolipoprotein A-1 and gelsolin. There are now at least 36 point mutations in the TTR gene associated with FAP and these continue to be described. Recent studies on the possible role individual point mutations in the TTR gene may play in amyloidosis have helped give us an insight into the mechanisms behind peripheral nerve amyloidosis. This article reviews the clinical and pathological features of the peripheral nerve amyloidosis and discusses theories of amyloidogenesis based on studies of FAP.