Protein aggregation is a ubiquitous concern during biopharmaceutical product formulation and process development. The process of nonnative aggregation has also attracted long-standing interest in fundamental disease studies due to its potential role in a growing number of chronic ailments such as Huntington’s Disease, Alzheimer’s Disease, and prion diseases. In both cases, there is evidence that the size, structure, and/or morphology of aggregates are important factors in the biological response(s) to aggregates in vivo. Aggregation of native or folded proteins is also a long-standing area of research, both as a possible approach for bio-separations, as well as its implications for limiting drug dosage or delivery options. This seminar focuses on experimental, modeling, and protein engineering approaches to control or predict the effects of mutations and solvent conditions on aggregation and self-assembly of therapeutic and model proteins. The importance of electrostatic interactions is highlighted by a number of examples, including aggregation mechanisms, phase behavior of aggregates (as opposed to monomers), and structural perturbations to the native state. These provide insights into rational formulation design, as well as different design paradigms to arrest or drive aggregation. A different approach to interpreting laser light scattering and related experiments is also proposed, that allows one to easily deal with both low and high concentration protein conditions, but highlights that “low” and “high” concentrations are not as simple a definition as conventionally accepted.