During the last one or two decades, monolithic polymers and silica have been developed for use as a new separation material or as a solid phase extraction sorbent and the applications with monoliths have been dramatically increased to separate the analytes by HPLC and to extract the analytes by solid phase extraction. The structure of monoliths differs from those of conventional particle materials. Specifically, the porosity of monoliths is over 80% and is larger than that of silica particle materials; therefore, columns packed with monoliths provide fast and high throughput analysis. Furthermore, high flow analysis is possible using monoliths because they produce very low back pressure. The applications of HPLC using monoliths for separation of bio-active compounds have gradually increased. In this review, these applications are summarized so that researchers can be introduced to the advantages of using monolithic silica. In addition, monolithic materials have the potential to be used as conventional solid phase extraction sorbents for the extraction of analytes in a sample matrix. The analytes in the sorbent can be eluted with a small volume because the monolith has wider surface area for each unit volume than those in other silicas or polymers and the required volume of the sorbents to extract the analytes is smaller in comparison with the conventional methods. To utilize these advantages of monoliths, new devices have been developed. In this review, the applications of monolithic silica for the extraction of drugs and medicines in biological materials are summarized.