According to genetic engineering legislation in Switzerland, the cultivation of genetically modified plants (GMPs) must be accompanied by environmental monitoring. This environmental monitoring is intended to identify any negative effects on the environment as early as possible so that necessary remedial measures can be taken. Accordingly, the authorities must be in a position to recognise changes in the environment and classify them as environmental harm. In our opinion, however, environmental monitoring is only partially suitable for reducing uncertainties which might still exist after the risk assessment of GMPs. From a scientific point of view, there are four difficulties with such decisions. The first three difficulties concern methodological limitations in scientific data collection. The fourth difficulty stems from the controversial assessment of the environmental effects of GMPs. Thus, it is nowadays unclear just which environmental changes are effectively to be evaluated as constituting harm. In this article, we analyse the four challenges and suggest possible strategies for countering them. Any remaining uncertainties should ideally be investigated during risk assessment before approval is granted. Regulatory authorities should recognise the limitations of environmental- monitoring programs for decision-making during cultivation of GMPs.