The design of space missions faces resource limitations that may severely restrict the extent of ground-based calibration programs. Ensuring that the knowledge requirements on key scientific performance are commensurate to the scientific goals of a mission is therefore crucial. In this paper, we describe a method to verify the adequacy of the X-ray effective area calibration requirements and apply it to the mirrors of Athena, the next large-class X-ray observatory of the European Space Agency. It is based on a Monte Carlo algorithm producing a set of energy-dependent mirror effective areas, which describe the limitations in our knowledge of the true performance as embedded in the calibration requirements. Applying this method to a number of simplified astrophysical scenarios related to the “hot and energetic” science themes of Athena, we conclude that the current calibration requirements of the mirror effective area are commensurate to the driving scientific requirements. Our results also stress the need to fulfill, or possibly to exceed the calibration requirements on the relative effective area to ensure fidelity in the reconstruction of X-ray, broad-band spectral features, e.g., those expected from the reflection by relativistic accretion disks around accreting black holes.