OBJECTIVES: This systematic review aimed to comprehensively collect and summarise the current body of knowledge regarding the cost-of-illness of amyotrophic lateral sclerosis, to identify cost-driving factors of the disease and to consider the development of costs over the course of disease. Further, the review sought to assess the methodological quality of the selected studies. METHODS: A systematic review was performed using the databases MEDLINE, Embase, Cochrane Library and PsycINFO. Studies examining the economic burden of amyotrophic lateral sclerosis on a patient or national level written in English or German published from the year 2001 onwards were included. Additional searches were conducted. Study characteristics and results were extracted and compared. RESULTS: In summary, 20 studies were included in this review. Most studies investigated costs per patient, amounting to total costs between €9741€ to €114,605. Six studies confirmed a rise in costs with disease progression, peaking close to the death of a patient. National costs for amyotrophic lateral sclerosis varied between €149 million and €1329 million. CONCLUSION: Most of these studies suggest the economic burden of amyotrophic lateral sclerosis to be considerable. However, further research is needed to establish a cost-effective health policy in consideration of disease severities.