Post-market monitoring (PMM) protocols should ensure the detection and prevention of adverse effects on the environment possibly deriving from commercial cultivation of genetically modified (GM) crops. A need to define the conditions and measures required for PMM on a scientific, legal, and administrative basis has become apparent, particularly since the cultivation area of Bt-maize in the European Union (EU) has gradually increased over the last years. Although several conceptual proposals have been made on how PMM programmes could be designed, as yet, there is no general consensus on how PMM protocols of Bt-maize could be implemented in practice to lead to results that can be used for regulatory decision-making. This lack of consensus inevitably leads to a certain confusion regarding decisions on the implementation of appropriate risk management measures. Although conceptual differences between case-specific monitoring (CSM) and general surveillance (GS) have been identified, it seems that the distinction between the two programmes still remains blurred among many actors involved in the discussion. Particular ambiguity remains concerning the question of how far results obtained in pre-market risk assessment (PMRA) have to be confirmed by CSM and what conditions are necessary to select either a CSM- or a GS-approach when addressing a particular potential risk. The present paper aims at reviewing the conceptual bases of PMM by emphasizing both the role of PMRA data and the differences between CSM and GS when designing appropriate PMM protocols for Bt-maize. The challenges in obtaining significant scientific data for decision-making are discussed using an approach to monitor potential environmental effects on natural enemies.