The range of possible interpretations of the phrase “appropriate representation” has left investigators struggling with the practical application of the National Institutes of Health guidelines on the inclusion of minorities in research. At least three goals might be reached by including minorities in clinical research: to test specific hypotheses about differences by race and ethnicity; to generate hypotheses about possible differences by race and ethnicity; and to ensure the just distribution of the benefits and burdens of participation in research, regardless of whether there are expected differences in outcome by race or ethnicity. In this paper, we describe possible interpretations of “appropriate representation,” as well as provide a general approach that investigators might use to address this issue. To expand scientific knowledge about the health of minority populations, investigators should be expected to state which goal they have selected and why that goal is appropriate as compared with other possible goals.