Chloramphenicol (CAP) is a broad-spectrum antibiotic, effective against a wide range of microorganisms, and has widely been used since the 1950s to treat food-producing animals. However, CAP has been rapidly associated to serious toxic effects, especially bone marrow depression, particularly severe when it assumes the form of the doseindependent and fatal aplastic anaemia. The well-known risk of irreversible bone marrow disorders and the absence of safe residue levels has determined European Union (EU) prohibition for veterinary use, in 1994, and no maximum residue limit (MRL) has been established for this antibiotic. Despite this legal ban, CAP has recently been found in several animal-derived foods, mainly aquaculture products. In order to prevent illegal use, it is important to develop analytical methodologies that provide performance limits capable of detecting and quantifying residual levels of this antibiotic. In this paper, the authors present a review of the most relevant procedures for sampling, pre-treatment, extraction/purification and determination of CAP residues in different food matrixes, published in the literature for the past decade. A special focus will be given to gas chromatography - mass spectrometry (GC-MS) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), as they represent the most modern and reliable analytical methodologies for determination of CAP residues.