Postoperative nausea and vomiting (PONV) are the most frequent side-effects in the postoperative period, impairing subjective well-being and having economic impact due to delayed discharge. However, emetic symptoms can also cause major medical complications, and post-craniotomy patients may be at an increased risk. A review and critical appraisal of the existing literature on PONV in post-craniotomy patients, and a comparison of these findings with the current knowledge on PONV in the general surgical population, leads to the following conclusions: (1) Despite the lack of a documented case of harm caused by retching or vomiting in a post-craniotomy patient, the potential risk caused by arterial hypertension and high intra-abdominal/intra-thoracic pressure leading to high intracranial pressure, forces to avoid PONV in these patients. (2) There is unclarity about a specifically increased (or decreased) risk for PONV in post-craniotomy patients compared with other surgical procedures. (3) The decision whether or not to administer an antiemetic should not be based primarily on risk scores for PONV but on the likelihood for potential catastrophic consequences of PONV. If such a risk cannot be ruled out, a multimodal antiemetic approach should be considered regardless of the individual risk. (4) Randomized controlled trials with antiemetics in post-craniotomy patients are limited with respect to sample size and methodological quality. This also impacts upon the meaning of meta-analyses performed with trials that showed marked heterogeneity and inconclusive results. (5) No studies on the treatment of established PONV are available. This highlights the need to transfer knowledge about PONV treatment from other surgical procedures. (6) Despite the possibility that PONV in post-craniotomy patients can be triggered by specific conditions (e.g. surgery near the area postrema at the floor of the fourth ventricle with the vomiting centre located nearby), recommendations based on trials in post-craniotomy patients may be flawed. Thus, general knowledge on prevention and treatment of PONV must adopted for craniotomy settings.