Objective: Central sensitization (CS), a mechanism explaining the persistence of symptoms, has been the focus of many research projects. Explanations given to patients with chronic pain are often based on this mechanism. It is hypothesized that CS also plays an important role in the persistence of medically unexplained symptoms (MUS). However, definitions and operationalizations of CS vary. We conducted a systematic review of definitions, operationalizations and measurement instruments of CS. Methods: We searched in PubMed, EMBASE, PsycINFO, Cinahl and The Cochrane Library till September 2017 and included papers that addressed CS in relation to chronic pain and/or MUS. Two reviewers independently selected, analysed and classified information from the selected publications. We performed a thematic analysis of definitions and operationalizations. We listed the measurement instruments. Results: We included 126 publications, 79 publications concerned chronic pain, 47 publications concerned MUS. Definitions of CS consistently encompass the theme hyperexcitability of the central nervous system (CNS). Additional themes are variably present: CNS locations, nature of sensory input, reduced inhibition and activation and modulation of the NDMA receptor. Hyperalgesia and allodynia are widely mentioned as operationalizations of CS. Quantitative sensory testing (QST) and (f)MRI are the most reported measurement instruments. Conclusions: There is consensus that hyperexcitability is the central mechanism of CS. Operationalizations are based on this mechanism and additional components. There are many measurement instruments available, whose clinical value has still to be determined. There were no systematic differences in definitions and operationalizations between the publications addressing MUS and those addressing chronic pain.