Background: Precision medicine has become part of oncology, with implications for therapy selection, treatment avoidance, dosing, and risk prediction. The presence of clinically predictive germline variants has also opened the hope that objective predictors of patient toxicity will be in the future. This is an opportunity for oncology, where selection from amongst apparently equal supportive care treatment options can be subjective. Methods: The incidence of genetic risk for untoward drug effect was characterized in 1193 consecutive patients submitted for clinical pharmacogenetics testing using a 50 gene panel. Not all were cancer patients, so this reflects a potential patient population. For each patient, the need to stop/avoid, adjust dose, and select an alternate medication was determined for the treatment of pain (CYP2D6, CYP1A2, OPRM1), nausea/vomiting (CYP2D6), antifungal prophylaxis (CYP2C19) or depression (CYP2D6, CYP2C`9). It is recognized that there are many sources of variation in the response and toxicity to these classes of medications. Results: Of the 1193 patients, 173 (14.5%) would have a recommendation to avoid oxycodone, codeine, or tramadol therapy and a non-standard dosage for 893 patients (75%). A change in antiemetic would be suggested for 35 patients (3%). If voriconazole antifungal prophylaxis was clinical required, 289 (24%) would need a dose increase, while 45 (3.8%) should be switched to a different regimen. The majority (759 patients; 64%) should avoid some of the commonly used agents for depression because of lack of efficacy or heightened risk of toxicity, while 195 patients would need a dose adjustment. Conclusions: Pharmacogenetics markers that put patients at risk for lack of efficacy or toxicity to supportive care medications was commonly observed. Thankfully there are many options for most supportive care areas, allowing genetic information to help focus treatment selection. In addition, for number of supportive care medications we do not know the sources of variable response, genetic or otherwise. There are opportunities to apply precision oncology principles to patient management now, while research helps toward the goal of objective medication selection.