Degradation of the materials in organic light-emitting devices (OLEDs) is the major impediment for the development of economically feasible, highly efficient and durable devices for commercial applications. Even though this chemical degradation is complex and the least understood of the different degradation modes in OLEDs, scientists were successful in providing insight into some of the responsible processes. In this progress report we will review recent advances in the elucidation of chemical degradation mechanisms: First possible reasons for defect formation and the most common and important methods to investigate those processes are covered before discussing the reactions and their products for the different types of materials present in a device. We summarize commonalities in the occurring mechanisms, and identify structural features and moieties that can be detrimental to operational stability. Some of the resulting implications on the development of new materials are presented and backed by concrete examples from literature.