This article reviews recent experiments on the modification of thiol-derived self-assembling monolayers (SAMs) by electron and x-ray irradiation. Several complementary experimental techniques such as near-edge x-ray absorption fine structure spectroscopy, x-ray photoelectron spectroscopy and microscopy, and infrared reflection absorption spectroscopy were applied to gain a detailed knowledge on the nature and extent of irradiation-induced damage in these systems. The reaction of a SAM to electron and x-ray irradiation was found to be determined by the interplay of the damage/decomposition and cross-linking processes. Ways to adjust the balance between these two opposing effects by molecular engineering of the SAM constituents are demonstrated. The presented data provide the physical-chemical basis for electron-beam patterning of self-assembled monolayers to extend lithography down to the nanometer scale.