In protein aggregation disorders, we assume that, during the process of protein aggregation, different types of aggregated species (oligomers, protofibrils, fibrils, etc.) are formed, some of which can be toxic to cells/tissues/organs. Recent evidence from numerous studies in cell and animal models of disease suggest that oligomeric species of different proteins might be more toxic that the larger, fibrillar forms. However, we still lack definitive data on the nature of the toxic species, mostly due to our inability to detect and define the various protein species that form as protein aggregate. The terms used are often broad and do not capture inter-laboratory variation in protocols and methods used for the characterization of aggregates. Even antibody-based methods can be ambiguous, as antibodies are delicate tools. Therefore, systematic and interdisciplinary studies are essential in order to guide future developments in the field.