ABSTRACTMultiplex ligation‐dependent probe amplification (MLPA) is a recent technique for the relative quantitation of up to 40 to 45 nucleic acid targets. Due to its relative simplicity, low cost, and availability of laboratory‐developed and more than 300 commercially‐developed assays, MLPA has become more widely used for both research and diagnostic applications. The MLPA platform is now extensively applied for postnatal diagnosis of genetic disorders and has recently been used for prenatal diagnosis. The published uses of MLPA for prenatal diagnosis include detection of aneuploidies, common microdeletion syndromes and subtelomeric copy‐number changes, identification of marker chromosomes, and detection of familial copy‐number changes in single genes. This review describes the technique of MLPA in detail and offers considerations for the interpretation of results in the clinical diagnostic setting. © 2012 John Wiley & Sons, Ltd.