In long-term milling experiments, in a stirred media mill, a grinding limit where no further particle breakage occurs was identified. During mechanical stressing of the particles, defects are generated in the crystalline lattice, which allows real fracture of nanoparticles. Below a critical size, defects cannot be stored or generated in the crystallites and the overall limit of grinding is reached. This limit is strongly influenced by material properties and hardly affected by most of the process conditions. However, the breakage kinetics strongly depend on the process parameters and suspension conditions as long as the grinding limit is not reached. Based on these findings, two mechanisms of nanoparticle breakage are proposed. Proper choice of process parameters saves not only up to 90% of the energy input to reach the grinding limit but also leads to a higher product quality in terms of crystallinity and less milling bead wear. (C) 2010 American Institute of Chemical Engineers AIChE J, 57: 1751-1758, 2011