Potential drug-drug interactions occur in 54% of all ICU patients, which is two times more than the rate seen in patients on general wards. A limited set of 20 pDDI pairs is responsible for more than 90% of all pDDIs. Therefore, it is worthwhile to develop guidelines for the management of these specific pDDIs. As the vast majority of the interactions can be managed by monitoring, advanced clinical decision support systems linking laboratory data to prescription data may be an effective risk management strategy.