In the years since the introduction of MALDI, a number of approaches have been explored to enhance the effi ciency of laser desorption/ionization and to reduce the number of matrix‐related background ions that populate a MALDI spectrum. Some strategies have been to tailor the desorption/ionization properties of a matrix by combining two or more compounds or by modifying existing functional groups. Professor Hui‐Fen Wu's group has been actively exploring the use of nanoparticles both as a matrix additive and as the sole initiator of desorption/ionization. In this month's Special Feature, Prof. Wu's and co‐authors off er a perspective for using nanoparticles for interaction‐assisted laser desorption/ionization of protein signatures from microorganisms.