Pharmacogenetics (PG), the study of human genome function and its effects on drug response, represents an exciting approach for reducing adverse drug events and increasing therapeutic efficacy. However, there is no clear information of the potential impact of PG in the primary care setting. Therefore, a study was conducted to determine the frequency of use of medications under PG influence, including 16 PG adverse drug reaction (ADR)-associated medications, in the primary care setting. Patients and methods: A cohort of 607 consecutive patients was accrued over a 3-month period from three primary care practices. Patients were asked to answer a verbal survey of demographics and medication use during the past 12 months. The survey specifically evaluated 16 drugs known to commonly cause ADRs and undergo metabolism by polymorphic enzymes. Patients also disclosed information on all other medication use in the last year. Medication use was verified by chart review. The primary outcome was the frequency of medication use. Results: Among the 16 ADR-associated medications, patients used analgesics (88.5%), antihypertensives (14.3%) and antidepressants (9.6%) most commonly. Overall, 28.6% of patients took more than one of the PG ADR-associated medications. Neither gender nor race appeared to influence the frequency of use of these medications (p = 0.5 and p = 0.08, respectively). Patients taking one or more of the drugs were older (p < 0.001). More patients seen for a chronic visit took one or more of the ADR-associated drugs than patients seen for an acute visit (35.8 versus 18.5%, p < 0.001). Discussion: This is the first attempt to describe the potential role of pharmacogenetics in the primary care setting. The findings indicate that at least one in four primary care patients take at least one medication that commonly causes adverse drug reactions due to genetic variability in drug metabolism, indicating that there is a potential role of pharmacogenomics in primary care. Nearly every patient was on a medication with putative PG association. Conclusions: Studies of the ability of PG should not be limited to medical subspecialties, as there is a great potential impact of PG on the primary care setting.