A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether methylene blue (MB) is of benefit in treating adult patients who develop catecholamine-resistant vasoplegic syndrome (VPS) during cardiac surgery. Altogether 47 papers were found in Medline and 107 in Embase using the reported search. A further five papers were found by hand-searching reference lists. Four papers represented the best evidence on the subject and details of authors, journal, date and country of publication, patient group, relevant outcomes and weaknesses were tabulated. In addition, a further 14 papers are referenced to aid the discussion. We conclude that MB may provide an interesting and novel therapeutic option for adult patients who develop catecholamine-resistant VPS during cardiac surgery. Whilst there is currently insufficient evidence to advocate its use as first-line therapy it should be considered as a possible 'rescue therapy' in catecholamine-resistant VPS and some work has suggested that it may have a prophylactic role in preventing VPS. However, further large well-controlled studies are required before its routine use can be recommended.