Monoclonal antibodies are susceptible to chemical and enzymatic modifications during manufacturing, storage, and shipping. Deamidation, isomerization, and oxidation can compromise the potency, efficacy, and safety of therapeutic antibodies. Recently, in silico tools have been used to identify liable residues and engineer antibodies with better chemical stability. Computational approaches for predicting deamidation, isomerization, oxidation, glycation, carbonylation, sulfation, and hydroxylation are reviewed here. Although liable motifs have been used to improve the chemical stability of antibodies, the accuracy of in silico predictions can be improved using machine learning and molecular dynamic simulations. In addition, there are opportunities to improve predictions for specific stress conditions, develop in silico prediction of novel modifications in antibodies, and predict the impact of modifications on physical stability and antigen-binding.