Facial expressions of pain are not undefined grimaces but they convey specific information about the internal state of the individual in pain. With this systematic review we aim to answer the question of which facial movements are displayed most consistently during pain. We searched for studies that used the Facial Action Coding System (FACS) to analyze facial activity during pain in adults, and that report on distinct facial responses (Action Units, AUs). Twenty-seven studies using experimental pain and 10 clinical pain studies were included. We synthesized the data by taking into consideration (i) criteria used to define whether an AU is pain-related; (ii) types of pain; and (iii) the cognitive status of the individuals. When AUs were selected as being pain-related based on a "pain>baseline" increase, a consistent subset of pain-related AUs emerged across studies: lowering the brows (AU4), cheek raise/lid tightening (AUs6_7), nose wrinkling/raising the upper lip (AUs9_10) and opening of the mouth (AUs25_26_27). This subset was found independently of the cognitive status of the individuals and was stable across clinical and experimental pain with only one variation, namely that eye closure (AU43) occurred more frequently during clinical pain. This subset of pain-related facial responses seems to encode the essential information about pain available in the face. However, given that these pain-related AUs are most often not displayed all at once, but are differently combined, healthcare-professionals should use a more individualized approach, determining which pain-related facial responses an individual combines and aggregates to express pain, instead of erroneously searching for an uniform expression of pain.