It is known that microbial stress mechanisms play a significant role in short-term microbial adaptation to environmental perturbations, and activation of these mechanisms enhance a cell's chance for surviving the perturbation with minimal damage. Although the target of these mechanisms is protective at the cellular level, the effect may be disruptive at the macroscopic level in engineered bioreactor systems. In this paper, it is proposed that these mechanisms are activated in response to wastewater influent perturbations and may be a significant cause of activated sludge treatment process upset. Selected microbial stress responses are reviewed and hypotheses indicating their potential role in treatment process upset are proposed. A research approach that was previously used to identify the mechanistic cause of deflocculation during perturbation by electrophilic chemicals is summarized, and a protocol for future experiments geared toward establishing source-cause-effect relationships for a range of wastewater upset conditions is put forth. Identifying source-cause-effect relationships will provide a basis for development of new monitoring technologies and operational strategies for systems under the influence of influent chemical perturbations.