This review presents the state-of-the-art techniques that couple liquid chromatography (LC) and mass spectrometry (MS) via atmospheric pressure photoionization (APPI). The different ionization mechanisms are discussed as well as the influence of the mobile phase composition, the nature of the dopant, etc. A comparison with other ionization sources, such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), is reported, and the combination of APPI with these sources is also discussed. Several applications, covering the time period of 2005-2008, for the analysis of drugs, lipids, natural compounds, pesticides, synthetic organics, petroleum derivatives, and other substances are presented.