Several methodology issues concerned with the use of biologic markers for epidemiological research studies were discussed in this review. The impact biologic markers have had on epidemiologic research includes the ability to quantify indicators of dose, early effects, predisposition, or confounding which can supplement or replace the nominal and ordinal categories. Biologic markers allow for the resolution of more detail in exposure disease associations. Sometimes biologic markers have caused a change to be made in the unit of analysis from the whole person to the cellular or molecular level. Even though the development and use of biologic markers has increased rapidly, the validity and meaning of many of the markers remain to be established. When analyzing biologic markers, the author urges that great care be taken not to be deceived by the extensive variation in biochemical individuality. Specific concerns for case control, cohort and intervention studies were noted. Ethical issues were considered as they relate to the design and conduct of studies, the interpretation, communication and use of study results, and legal issues.