Proteome stability constitutes an essential aspect of protein homeostasis (proteostasis). Proteostasis networks maintain proteins and their interactors in a defined conformation for their activity, localisation, and function. However, endogenous or exogenous stressors can perturb proteostasis integrity and deplete folding capacity, generating destabilized folding intermediates and deleterious aggregated species. Over the years, protein unfolding, misfolding and aggregation have been reported to be associated with aging and many diseases such as neurodegenerative diseases, diabetes, cardiac disease and toxicity, and cancers. Therefore, monitoring proteome stability is central to understanding underlying biological processes and mechanisms of disease progression. Herein, we review the recent bioanalytical methods to measure protein stability in cells on a proteome-wide scale.