Several types of headholders are routinely used in neurosurgical practice to secure the head in a precise position, providing better security during surgical dissection as well as an absence of eye compression during prone positions. Nevertheless, potentially lethal complications might occur. We performed a review of the literature via PubMed and Google Scholar using the terms “Mayfield skull clamp”, “Sugita headholders”, “headholder complications” and “skull clamp complications”. Twenty-six complications directly related to the use of headholders were identified through 19 papers published from 1981 to 2014: mainly skull fractures with or without a dural laceration (50%), epidural hematomas (23.8%), skull fractures with or without a dural laceration (50%), and air embolism (9.5%). The authors propose recommendations for the safe use of headholders.