The effective treatment of emetic complications of cancer therapies has remained a challenging task for cancer patients and their cancer care providers. Despite striking advances in antiemetic interventions, the need for more personalized targeted treatments in those who fail to response to the currently available antiemetic agents are yet to be met. Casopitant, a potent selective inhibitor of neurokinin-1 receptors, is a product of the increasingly heightened interest in this particular subset of cancer patients. The current review examines the emerging data about the benefits and safety of casopitant for treatment of chemotherapy-induced acute and delayed emesis, as well as the postoperative nausea/vomiting. Although preclinical studies promoted the notion of a potential superiority of casopitant over the already approved aprepitant in enhancing food and fluid intake, the limited comparison in clinical settings have yet to affirm a demonstratable meaningful superiority. The prevailing view from the published prospective studies supports a single 100 or 150 mg dose schedule of casopitant, orally or intravenously, as an effective and safe prophylaxis for acute and delayed emesis. The relative inferior outcomes of "nausea" control, as compared to a more impressive "vomiting" prevention, are similarly shared by both casopitant and aprepitant. This repeated and disappointing observation has challenged the precision and accuracy of our current understandings about the exact fabric of the "emesis axis." The future efforts should be directed to identify more effective agents for managing nausea and anticipatory emesis equally in both genders.