Chemiluminescence (CL)-based detection has become in the last years quite a useful detecting tool in liquid chromatography (HPLC) due to its simplicity, low cost and high sensitivity and selectivity, and the development in instrumentation. Minimal instrumentation is required and no external light source is needed; thus, the optical system is quite simple. As a consequence, a wide variety of analytical methods have been developed in clinical, pharmaceutical, environmental and food analysis. In this review, applications of the HPLC-CL coupling in those different fields have been included and classified in relation to the different CL systems employed (namely peroxyoxalate reaction, tris(2,2'-bipyridine) ruthenium (II) reaction, luminol system and direct oxidations) and also sub-classified according to the group of analyte. The review covers the literature from 2000 until the end of 2008.