One of the most dreaded side effects of anticancer treatment, chemotherapy-induced nausea and vomiting (CINV) plays a significant role in cancer patients' morbidity and quality of life. The management of CINV has been refined over the past several decades, and CINV can now be addressed with targeted prophylactic medications aimed at inhibiting the molecular pathways involved in emesis, including serotonin receptor antagonists and neurokinin-1 receptor antagonists. Advances in the understanding of the physiology of CINV, coupled with the introduction of several agents that inhibit activation of these receptors, are reflected in current CINV guidelines. These guidelines, which are largely similar, provide recommendations based on expert review of available clinical trial data. Despite the availability of effective prophylaxis, many patients still suffer from CINV. To minimize these side effects, clinicians should ensure widespread adoption and implementation of at least 1 CINV guideline in their practice. Even when the recommendations are followed, a small group of patients continue to experience CINV, often in the form of nausea, for which few treatments are effective. Current and future studies will begin to delineate the specific pathways for the development of nausea, hopefully leading to the identification of novel agents and regimens with improved efficacy in this setting.