In the first 2 articles of this series, we reviewed the basic genetics concepts necessary to understand genetic association studies, and we enumerated the major issues in judging the validity of these studies. In this third article, we review the issues relating to the applicability of the results in the clinical situation. How large and precise are the associations? Many genetic effects are expected to be smaller in magnitude than traditional risk factors. Does the genetic association improve predictive power beyond easily measured clinical variables? In some cases, the additional genetic information adds only a small increment in the predictive ability of a diagnostic or prognostic test. What are the absolute vs relative effects? Even if the genetic risk is high in relative terms, the baseline risk may be very low in absolute terms. Is the risk-associated allele likely to be present in my patient? A risk allele may have a strong effect but be rare in a particular ethnic group. Is the patient likely better off knowing the genetic information? Given that genes cannot be modified, one must weigh whether the genetic information is likely to be helpful in planning other health interventions or initiating behavior change.