This article on pharmacoepidemiology, the second of two parts, is a more focused discussion of the methodology of cohort studies and case-control studies, the basic methodologies of which were discussed in part I. The nested case-control study incorporates the strengths of both the cohort and case-control studies but may alleviate some of the methodologic challenges inherent in both types of studies. In a nested case-control study, a cohort of individuals is followed during certain time periods until a certain outcome is reached. The analysis is conducted as a case-control study in which cases are matched to only a sample of control subjects. Matching allows for control of potential confounding variables such as age, calendar time, and disease duration. Also, the time dependency of an exposure can be quantified without complicated statistical techniques. Matching the cases and controls by time allows the investigator to stratify exposure based on current, past, or intermittent use. By using the principles of epidemiology, the nested case-control study allows for the control of confounding variables, as well as better quantification of time-dependent exposures.