The high-molar-mass chemical species, macromolecules, represent the very important constituents of both organic and inorganic or natural and synthetic environments-from the living organisms, clays, and earth constituents to numerous synthetic objects such as the most rubbers, bers, coatings, constructing materials, adhesives, etc. The separation and molecular characterization of macromolecules represents a demanding challenge for science, technology, and everyday life. For synthetic polymers, liquid chromatography is presently the most important tool for separation and molecular characterization. In this chapter, which is oriented to the everyday analytical practice, fundamentals of high-performance liquid chromatography of synthetic polymers (polymer HPLC) are presented. The differences between HPLC of small molecules and macromolecules are elucidated so that the experts from both elds can nd the necessary information to make comparisons. The researchers in the area of polymer synthesis and application would acquire the basic knowledge about the potential and limitations of polymer HPLC: the former is often overestimated while the problems are neglected. Therefore, the present level of polymer HPLC is being critically assessed in this chapter and the necessity for further renements and innovations is evidenced. Some anticipated future developments are also outlined. One of the objectives of this chapter is to help experimental workers in devising the optimum HPLC procedures for solving the particular separation/ characterization tasks in polymer research and technology. This latter objective is accentuated by the unconventional organization of the text with numerous cross-quotations, which are intended to simplify the orientation of readers. In order to make the reading as easy as possible, examples of numerous practical applications are largely omitted; these can be found in the quoted references, especially in numerous monographs, handbooks, collections of papers, chapters in books, and review papers, for example [1-33]. It is amazing to nd that many fundamental ideas and observations published in the rst stages of the polymer HPLC development are overlooked or oblitered by some authors of new reviews and original studies. Honor is often not paid to the founders of certain methods, and numerous already published ideas are “re-discovered.” Therefore, numerous references to the breakthrough articles and older books, reviews, and original papers are also included in this chapter. History of the particular procedures of polymer HPLC can be traced on the basis of those publications. It is also hoped that some forgotten ideas will be revived, and eventually brought to an application, taking advantage of a general progress in the theory, materials, and technology. The author apologizes to the pioneers not mentioned here: the limited scope of this chapter, short time available for the compilation, and difcult access to the literature-not the intention-are the reasons.