Clioquinol is used for treatment of amoebiasis and infection with Dientamoeba fragilis. In a guideline of the Dutch Working Party on Antibiotic Policy, clioquinol is recommended as a first-choice treatment for Dientamoeba fragilis. This drug, however, is associated with subacute myelo-optico-neuropathy (SMON). It was withdrawn from the market worldwide in 1985 by manufacturer Ciba-Geigy. Although the Dutch Medicines Evaluation Board has registered no products for systemic use of clioquinol since then, the drug is available as a pharmacy-compounded drug and the last few years the use of clioquinol in the Netherlands has risen again. The Netherlands Pharmacovigilance Centre Lareb has received a growing number of reports of adverse drug reactions (ADRs) associated with the use of clioquinol, including nervous system disorder ADRs occurring at recommended dosages. Therefore, we debate the use of clioquinol as a first-choice treatment option for Dientamoeba fragilis.