The wild poses a multifaceted challenge to the maintenance of cellular function. Therefore, a multistressor approach is essential to predict the cellular mechanisms which promote homeostasis and underpin whole-organism tolerance. The intertidal zone is particularly dynamic, and thus, its inhabitants provide excellent models to assess mechanisms underpinning multistressor tolerance. Here, we critically review our current understanding of the regulation of the cellular stress response (CSR) under multiple abiotic stressors in intertidal organisms and consider to what extent a multistressor approach brings us closer to understanding responses in the wild. The function of theCSR has been well documented in laboratory and field exposures with a view to understanding single-stressor thermal effects. Multistressor studies still remain relatively limited in comparison but have applied three main approaches: (i) laboratory application of multiple stressors in isolation, (ii) multiple stressors applied in combination, and (iii) field-based correlation of multiple stressors against the CSR. The application of multiple stressors in isolation has allowed the identification of putative,shared stress pathways but overlooks non-additive stressor interactions on the CSR. Combined stressor studies are relatively limited in number but already highlight variable effects onthe CSR dependent upon stressor type, timing, and magnitude. Field studies have allowed the identification of responsive components ofthe CSR to various stressors in situ but are correlative, not causative. A combined approach involving laboratory multistressor studies linkingthe CSR to whole-organism tolerance as well as field studies is required if we are to understand the role ofthe CSR in the natural environment.