There have been few studies to determine whether the efficacy of antiemetics is maintained over repeated courses of cisplatin chemotherapy. Two large controlled studies have been undertaken by our group to address this issue. A comparison of the standard high-dose regimen of metoclopramide plus methylprednisolone versus a higher dose regimen of metoclopramide plus dexamethasone and diphenhydramine showed that the latter regimen was significantly more efficacious with regard to complete control of nausea and vomiting in chemotherapy-naïve patients. However, this difference was not maintained over repeated courses of chemotherapy. A comparison of metoclopramide and dexamethasone plus diphenhydramine with ondansetron plus dexamethasone showed that the ondansetron regimen provided even greater control of vomiting, which was maintained over subsequent cycles of chemotherapy. Various factors were analysed in both studies to determine whether they had any effect on treatment outcome. In general, age < 50 years, female gender, and higher doses of cisplatin were associated with an increased risk of emesis. However, the most significant prognostic factor was emesis response in the previous cycle. It is therefore important to aim for good antiemetic control in the first cycle of cisplatin chemotherapy.