This article is the first of two parts on pharmacoepidemiology, a relatively new science that explores drug efficacy or toxicity using large observational study designs. The number of pharmacoepidemiologic studies published in medical journals has increased, as these studies have explored drug-related questions that at times cannot be answered in randomized clinical trials. Four pharmacoepidemiologic study designs will be discussed that explore the association between a specific pharmacologic agent and a disease of interest: cohort studies, case-control studies, case-crossover studies, and case-time-control studies.