High performance liquid chromatography (HPLC) is an integral analytical tool in assessing drug product stability. HPLC methods should be able to separate, detect, and quantify the various drug-related degradants that can form on storage or manufacturing, plus detect and quantify any drug-related impurities that may be introduced during synthesis. Forced degradation studies (chemical and physical stress testing) of new chemical entities and drug products are essential to help develop and demonstrate the specificity of such stability-indicating methods. In addition to demonstrating specificity, forced degradation studies can be used to determine the degradation pathways and degradation products of the APIs that could form during storage, and facilitate formulation development, manufacturing, and packaging. Procedures for the preparation of specific degradation products needed for method validation often emerge from these studies. For marketing applications, current FDA and ICH guidance recommends inclusion of the results, including chromatograms of stressed samples, demonstration of the stability-indicating nature of the analytical procedures, and the degradation pathways of the API in solid state, solution, and drug product. The chemical structures of significant degradation products and the associated procedures for their isolation and/or characterization are also expected to be included in the filing. The experimental protocol for performing forced degradation studies will depend on the active ingredients and formulation involved because the chemistry of each compound is different. In general, a target of approximately 10% degradation of the API during forced degradation, or exposure to energy in slight excess of what is typically used in accelerated storage is recommended. In this way, the “worst-case” degradation products can be studied. The following will provide some suggestions for performing forced degradation studies based upon available guidance from the ICH and FDA.