Detailed safety review of the intestinal anthelminthics (pyrantel and niclosamide) and antischistosomal and antitrematodes (oxamniquine and triclabendazole) was conducted using publications in journals and major reference sources combined with the assessment of adverse drug reaction (ADR) reports in the database of the WHO Collaborating Centre for International Drug Monitoring in Sweden. Data from available limited publications on the subject provide evidence in support of the overall safety of these medicines with no publication citing an unfavourable safety assessment of any of the drugs. Whilst there have been concerns about the risk of seizures with oxamniquine, these concerns have not diminished the extent to which the medicine has been used in several countries. All four medicines appear to be safe and well tolerated even when used in mass treatment campaigns in several countries. This safety review indicates that oxamniquine, triclabendazole, niclosamide and pyrantel have favourable benefit–risk profiles for use in humans. However, in order to enhance the evidence base to determine safety issues in relation to medicines that are used heavily in settings with poor or non-existent pharmacovigilance systems, it is recommended that the WHO pushes its current supportive efforts for the setting up of such systems globally, especially in resource-limited countries. The four drugs are all retained on the current list of the WHO Model List of Essential Medicines.