Interactions between phenytoin and the fluoropyrimidine derivatives, 5 fluorouracil (5FU) and capecitabine, are not commonly documented or widely recognised. As more people with significant medical comorbidities are now being considered for chemotherapy, it is increasingly likely that people receiving phenytoin will be prescribed treatment with fluoropyrimidines. We present two cases of clinical phenytoin toxicity occurring after starting treatment with 5-fluorouracil/folinic acid (5FU/FA) and a third who developed clinical phenytoin toxicity after starting capecitabine (an orally administered prodrug of fluorouracil).