The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) assessed the risks to human health related to the presence of palytoxin (PlTX)-group toxins in shellfish. PlTX-group toxins have mainly been detected in soft corals of the genus Palythoa and in algae of the genus Ostreopsis. Blooms of Ostreopsis spp. have recently been reported in some European countries. Occurrence of Ostreopsis spp. may result in contamination of shellfish intended for human consumption. Currently there are no regulations on PlTX-group toxins in shellfish, either in the European Union (EU), or in other regions of the world. The toxicological database of PlTX-group toxins is limited, comprising only acute toxicity studies for PlTX and ostreocin-D via several routes of administration in various animal species. The oral route was least sensitive. Acute toxicity and deaths have been reported from human outbreaks, but there are no reliable quantitative data on acute toxicity in humans. In view of the acute toxicity and the lack of chronic toxicity data for PlTX-group toxins, the CONTAM Panel was only able to derive an oral acute reference dose (ARfD) of 0.2 µg/kg b.w. for the sum of PlTX and its analogue ostreocin-D. In order for a 60 kg adult to avoid exceeding the ARfD a 400 g portion of shellfish meat should not contain more than 12 µg of the sum of PlTX and ostreocin-D, corresponding to 30 µg/kg shellfish meat. The mouse bioassay (MBA) has been used to detect PlTX-group toxins, but cell based assays have been developed as alternative. However, positive results require confirmation by chemical methods. High performance liquid chromatography-fluorescence detection (HPLC-FLD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods can be valuable tools for the determination, but method optimisation and validation as well as the development of certified reference materials and standards are necessary.