XRF is generally considered a nondestructive analytical method in the sense that a specimen is not altered by the analytical procedure. This study is related to paintings and illuminated manuscripts, where the analytes are often inorganic pigments embedded into organic matrices such as fabrics (canvases), paper or parchment, binders, and varnish. We found that a typical measurement cycle with conventional tubes and energy dispersive systems (e.g., 100 s, 100 W tube-power) causes no visible harm. However, 3 kW radiative power for several minutes and more (as often required for wide angle scans as well as for the analysis of light elements or traces in a wavelength dispersive spectrometer) can leave visible traces of permanent yellowing, brittleness, and even mechanical decomposition. In such cases scanning electron microscopy-images indicate permanent alteration of the cellulose fibers and, in paper, of the binder. Employment of modern X-ray optical devices which focus the photons of a wide beam onto a small spot may also leave visible (and invisible) traces of destruction.