The mechanisms and factors causing or influencing degenerative diseases require tailor-made solutions. Natural polysaccharides are among the most versatile building units of the novel drug delivery systems. Their properties can be easily tailored to specific needs because they depend not only on the first-order structure, but also on the molecular weight, the type of end-groups and the conformation of the chain. The review presents the current state-of-art in the field of modifications of natural polysaccharides aiming at improving the delivery of anti-degenerative agents. Derivatization includes introducing of ionic or hydrophobic groups in order to adjust polarity or to obtain amphiphilic material, as well as degradable bonds, spacers and targeting moieties. The influence of the modification on the properties of the carrier, such as its size, surface charge, encapsulation efficiency, drug release profile, and stability in vivo, is discussed. Application of the polysaccharide derivatives to enhance the mucoadhesion and to actively target the drug to its site of action is also shown for a variety of carriers: nano and microparticulate systems, coated liposomes, hollow particles and polymer-drug conjugates.