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 tools/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. The main criticisms surrounding pharmacoepidemiology research will also be investigated with a focus on the issue of bias and confounding. Briefly, common sources of pharmacoepidemiology data will also be discussed. This chapter will conclude with a mention of other tools that can be used for pharmacoepidemiology research including experimental studies designs and the systematic review/metaanalysis.