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Chemometrics is the chemistry field responsible for planning and extracting the maximum of information of experiments from chemical data using mathematical tools (linear algebra, statistics, and so on). Active pharmaceutical ingredients (APIs) can form impurities when exposed to excipients or environmental variables such as light, high temperatures, acidic or basic conditions, humidity, and oxidative environment. By considering that these impurities can affect the safety and efficacy of the drug product, it is necessary to know how these impurities are yielded and to establish the pathway of their formation. In this context, forced degradation studies of pharmaceutical drugs have been used for the characterization of physicochemical stability of APIs. These studies are also essential in the validation of analytical methodologies, in order to prove the selectivity of methods for the API and its impurities and to create strategies to avoid the formation of degradation products. This review aims to demonstrate how forced degradation studies have been actually performed and the applications of chemometric tools in related studies. Some papers are going to be discussed to exemplify the chemometric applications in forced degradation studies.