The pharmacological or toxicological efficacy of drugs can be influenced significantly when their metabolic pathway is induced or inhibited by co-administrated drugs.Metabolism-based drug-drug interactions (DDIs) have a high incidence and are important in clinical therapeutics. Studies on metabolism-based DDIs are now moved to the early stages of drug development, so that adequate assessment of its safety and effectiveness can be facilitated. These studies comprise in vitro and in vivo investigations and an appropriate design of studies is important. In many cases, negative findings from early in vitro and early clinical studies can eliminate the need for later clinical investigations. This article summarizes the background and mechanism of metabolism-based DDIs and focuses on the strategies of these studies.