Multidimensional chromatography is a technique where fractions from one chromatographic column are transferred to one or more chromatographic columns (or modes) for further separation. It is mostly used for better resolution of complex samples or for sample cleanup prior to analysis. The technique can be carried out off-line or on-line. The on-line technique is preferred for convenience, automation, and better quantitation. The off-line technique is best used when the solvents of the modes are not compatible or when the concentration of the components of interest are too low and require concentration prior to injection into the second column. This paper reviews multidimensional chromatography where the primary separation method is high performance liquid chromatography (HPLC) and the secondary technique is HPLC or gas chromatography (GC). On-line techniques are emphasized. Examples shown for LC/LC are pesticide in tomato plants and vitamins in protein food supplement, and for LC/GC a herbicide in sorghum using a unique interface.