Fear of the side effects of analgesic drugs frequently leads to the under-treatment of post-craniotomy pain. Nevertheless, this pain continues to be commonly observed, is frequently severe, and, if unrelieved, may cause distress for the neurosurgical patient and serious complications for the operative brain. We review recent evidence-based data on pain therapy after intracranial surgery. Especially when performed at the end of surgery, local anaesthetic scalp infiltration provides adequate, short-term postoperative pain relief. Opioids, such as morphine or oxycodone, may be used in the early period after craniotomy. If titrated properly, opioids do not increase serious side effects as compared with codeine. The non-narcotics ketoprofen, tramadol, and paracetamol may be useful as supplemental, opioid-sparing drugs. There is a need for larger trials to delineate safety and efficacy of analgesic therapies with a focus on short- and long-term outcomes.