Safety pharmacology is essential throughout the spectrum of drug discovery and development. Prior to first-in-human studies, safety pharmacology assays, tests, and models predict the clinical risk profile of a potential new drug. During clinical development, safety pharmacology can be used to explore--and potentially explain--both predicted and unpredicted side effects (e.g., adverse events, changes in vital signs, abnormal laboratory values) in order to refine the original clinical risk profile. This chapter will introduce the reader to safety pharmacology's role in translational medicine: the science of translating potential drugs' on- and off-target nonclinical properties to clinical consequences in order to select the best drug candidates to move into early clinical testing. Case studies will be used to illustrate the importance of safety pharmacology testing throughout all phases of drug development.