Reversed-phase liquid chromatography (RP-HPLC) has become a powerful and widely employed technique in the separation and analysis of a great variety of compounds with different functionalities. The most common type of stationary phase for RP-HPLC consists of nonpolar, hydrophobic organic species (e.g., octyl, octadecyl) attached by siloxane bonds to the surface of a silica support. In the first part of this article, a description of the many beneficial properties that make porous silica the most employed support in RP-HPLC will be presented, starting from the synthesis of silica. It is noteworthy that the chromatographic properties of the final column are strictly correlated to the preparation type. A silica surface possesses a number of attractive properties, but also some drawbacks. Unreacted or residual silanols interact with basic compounds and can induced peak tailing, which means a loss in chromatographic performance. This problem has lead many manufactures to produce stationary phases with reduced silanol activity which improve dramatically the peak shape of basic compounds. In the second part of this review, different approaches are proposed to obtain less reactive stationary phases.