Radiotherapy-induced nausea and vomiting (RINV) can be one of the most distressing symptoms of radiotherapy treatment, which if incompletely controlled may last for several weeks with fractionated radiotherapy and prevent completion of the planned treatment course. Current treatment guidelines recommend the use of 5-HT(3) receptor antagonists with or without corticosteroids for highly and moderately emetogenic radiotherapy, though only granisetron and ondansetron are currently indicated for RINV in most countries. Granisetron is a potent and highly selective 5-HT(3) receptor antagonist, with demonstrated efficacy in RINV in both placebo-controlled and comparative studies. In this paper the clinical experience with granisetron in RINV is reviewed, and its efficacy and safety compared with other antiemetic therapies.