Pharmacoepidemiology for postmarket drug safety research will be the primary focus of this chapter; however, the same methods can be used to conduct effectiveness research as well. First, the need for pharmacoepidemiology in postmarket drug safety research will be discussed, and then this chapter will go on to provide an in-depth review of the various epidemiologic designs that are commonly used for postapproval drug safety research, including the strengths and limitations of each, and also how to properly interpret results by performing an appropriate critical appraisal of the study.