Background - Chronic polyneuropathy is a common disorder with heterogenic clinical presentation and many different etiologies. Diagnostic investigation is challenging. Materials and methods - An algorithm for diagnostic investigation of chronic polyneuropathy is presented. It was designed to secure practical usefulness for general neurologists, identification of the most common causes with an adequate number of laboratory tests, and more focused investigation when necessary. The proposal is based on review of articles found by PubMed search using the terms peripheral neuropathy, cause, and investigation, relevant book chapters, and own clinical experience. Results - All patients should undergo a routine investigation for the most common causes of polyneuropathy by asking for diabetes, heredity, alcohol abuse, toxic medications and agents, symptoms of Sjogren's syndrome, renal failure, and the following laboratory tests; glucose, haemoglobin, leucocytes, thrombocytes, ESR, creatinin, ALAT, GT, vitamin B12, serum electrophoresis, TSH and thyroxin. If routine investigation is negative, a targeted approach based on clinical type and electrophysiological findings is recommended. The most common type with slowly progressive, symmetric sensory symptoms beginning in the feet can often be classified as cryptogenic without further investigation. Polyneuropathies with subacute onset, progressive weakness, asymmetric symptoms, proximal weakness, selective involvement of sensory fibers or demyelinating pathology, or other organ manifestations, have various etiologies that necessitate individual focused investigation. Interpretation - Diagnostic investigation of polyneuropathy can be simplified and systematized.