The interest in two-dimensional liquid chromatography (2D-LC) has been growing up since the last decades. This promising technique appears as a relevant solution for various analytical challenges encountered in pharmaceutical analysis.The objective of this review is to give an overview of past, current and emerging trends in 2D-LC techniques applied to pharmaceutical compounds. The referenced studies cover the late 1980s to the present. Information regarding the different aspects of this analytical technique, including chromatographic conditions, instrumental setup and compounds of interest, was compiled and summarized into a synoptic table. Particular attention is paid to key features including (i) the interfaces used for coupling the two dimensions, (ii) the application fields, and (iii) the chromatographic modes that can be combined together. Finally an attempt is made to predict future advances in two-dimensional separation techniqes for pharmaceutical analysis.