Amphibians are a suitable indicator group for monitoring possible negative direct or indirect effects of GMO cultivation at the individual and population level. Direct effects could occur in aquatic ecosystems via uptake of GM pollen or GM detritus by anuran larvae. However, indirect negative effects caused by changes in cultivation practices (changes in pesticide use, for instance) are more likely. The VDI Guideline 4333 aims to ensure comprehensive monitoring of the different life-stages of anuran species that are common in agricultural landscapes of Austria, Germany and Switzerland. The guideline includes a novel approach to tadpole monitoring. To assess immediate effects, tadpole, metamorph and adult deformation rates are compared with naturally occurring deformation rates. Adult population size, adult body condition and juvenile emergence are monitored over multiple years to assess long-term effects of GM crop cultivation on population viability. At each study site, monitoring has to be carried out at multiple amphibian breeding sites which differ in their exposure to GM crop cultivation. All monitoring data have to be stored in a central database for future meta-analyses. This will ultimately allow for generalized statements about the impact of GM crop cultivation on amphibians. Although specifically designed for GM crops, VDI Guideline 4333 may also serve as a model for studying the effects of a wider range of stressors on amphibian populations in agriculture and forestry.