This chapter addresses key issues for achieving safe reactor operation. Starting from conceptual measures that need to be considered during process development and plant planning, central thermoanalytical measurement methods and the stability of substances and interactions are presented. In terms of the design of safety-oriented process control, process-related criteria are named. Detailed information is provided for the design of the protective measures “pressure relief” and “limitation of reactant potential” used. Finally, an introduction to central techniques and methods for conducting safety and risk analysis is given.