Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles. Nowadays mass spectrometry-based approaches play a pivotal role in both detection and characterization of proteins. Here we describe two applications to study insoluble proteins: (a) hydrogen/deuterium exchange combined with mass spectrometry to analyze structural properties of amyloid fibrils and (b) the screening for inhibitors of the aggregation process by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.