This chapter focuses on the harmful pharmacological effects, referred to collectively as drug-induced liver injury (DILI). It reviews the major diseases of the liver and how they impact the primary liver tests. The chapter explains the toxicological effects that drugs have on the liver. This is followed by a review of the US Food and Drug Administration (FDA) guidance on the pre-marketing clinical evaluation of DILI and other clinical trial issues. The chapter presents classical statistical approaches to the detection of DILI in clinical trial data. It also presents ideas based on the use of stochastic process models to describe the dynamic (longitudinal) changes that occur when DILI exists in the study subject. The chapter further focuses on some of the statistical problems related to the evaluation of DILI in drug clinical trials. It also highlights that hepatic toxicity is a very important issue for the safe use of pharmaceuticals.