© 2017 Elsevier Ltd All rights reserved. Biomaterials interact with biological tissue through their surfaces. Therefore, the chemical composition and structure of biomaterial surfaces are of paramount importance to biomedical and tissue-engineering research and applications. The use of polymers to modify biomaterial surfaces offers the advantages of controlling interface architecture and introducing versatile chemical functionalities. Among several techniques of surface modification such as chemical grafting and self-assembled monolayers of organic molecules, layer-by-layer (LbL) assembly emerges as the most versatile technique of surface modification. The technique is most adaptive to the choice of substrate surface chemistry and allows incorporation of a wide variety of chemical functionalities into coatings. Importantly, recent demonstration of postassembly derivatization of LbL films into soft, hydrogel-like films, as well as in situ cross-linking of polymers during deposition using a click chemistry approach significantly increases the appeal of using LbL assembly for surface modification of biomaterials. In this chapter, we discuss fundamentals of LbL deposition of macromolecules at surfaces, structure of fabricated surface films, a wide range of mechanical properties of LbL surface coatings, as well as focus on synthesis and properties of LbL-derived surface hydrogels as a promising candidate for surface modification of biomaterial surfaces.