Clinical decision support systems (CDS) have an important role in the implementation of precision medicine, particularly for pharmacogenomics. This study examines potential factors for their acceptance by primary care clinicians. For this qualitative study we purposively selected five U.S. primary care sites with a variety of sizes, electronic health record vendors, and patients. We interviewed an average of seven clinicians per site. Clinicians placed a low priority on incorporating pharmacogenomics into practice. Other themes included the potential of precision medicine, clinician unfamiliarity with genomics, minimal evidence for primary care uses, additional costs and time burdens, workload, and a need to first successfully complete other electronic health record interventions. This study outlines issues in implementing primary care precision medicine and the role for genomic CDS. Currently there are signficiant barriers. With more evidence and the development of effective CDS, however, there is potential for turning each of the barriers into facilitators.