A systematic review of the available evidence examining the cost of work-related stress (WRS) would yield important insights into the magnitude of this social phenomenon. The objective of this review was to collate, extract, and synthesize economic evaluations of the cost of WRS to society. A research protocol was developed. Included cost-of-illness (COI) studies estimated the cost of WRS at a societal level, and were published in English, French or German. Searches were carried out in ingentaconnect, EBSCO, JSTOR, Science Direct, Web of Knowledge, Google, and Google scholar. Included studies were assessed against 10 COI quality assessment criteria. Fifteen studies met the inclusion criteria and were reviewed. These originated from Australia, Canada, Denmark, France, Sweden, Switzerland, the United Kingdom, and the EU-15. The total estimated cost of WRS was observed to be considerable and ranged substantially from US$221.13 million to $187 billion. Productivity related losses were observed to proportionally contribute the majority of the total cost of WRS (between 70 to 90%), with health care and medical costs constituting the remaining 10 to 30%. The evidence reviewed here suggests a sizable financial burden imposed by WRS on society. The observed range of cost estimates was understood to be attributable to variations in definitions of WRS; the number and type of costs estimated; and, in how production loss was estimated. It is postulated that the cost estimates identified by this review are likely conservative because of narrow definitions of WRS and the exclusion of diverse range of cost components.