These viruses depend on balancing the host ER stress responses to maximise beneficial processes in proteostasis, whilst minimising detrimental quality control and immune recognition systems. This balance is largely achieved through the direct specific effects of viral surface glycoproteins but can also be modulated by the indirect effects of other viral proteins. Furthermore, prolonged activation of the UPR in the respiratory system is generally detrimental for disease pathogenesis, further exemplified by the prevalence of chronic UPR activation in common co-morbidities and predisposing factors for respiratory viral diseases. The therapeutic potential of harnessing the UPR axis in treating respiratory viral diseases highlights the need to further our understanding of the complex interactions underlying ER stress in viral infection.