This chapter reviews the state-of-the-art about vanadiumâ phosphorus oxide (VPO) system employed as a heterogeneous catalyst in the selective oxidation of n-butane to maleic anhydride, which is the only industrial process of a selective vapor-phase oxidation of a light alkane. The VPO system has been intensively studied over the last two decades and significant fundamental insights into the mechanism of n-butane oxidation to maleic anhydride have been obtained. This chapter discusses conventional synthesis and solid-state chemistry of crystalline VPO phases, including VPO precursor synthesis and the nature of its thermal transformation into a selective and active VPO catalyst under catalytic reaction conditions. It then focuses on the surface structure of the VPO catalysts, the nature of proposed catalytic active and selective active sites, the role of surface promoters and alternative synthesis approaches to mesoporous, macroporous and other novel VPO phases that are promising for selective oxidation of light alkanes. These insights are critical for understanding molecular surface structureâ activity and â selectivity relationships and the rational design of improved VPO catalysts for the selective oxidation of n-butane to maleic anhydride.