Implantation of foreign materials can elicit an immune response proportional to the cytotoxicity of the material. Surface modification is an important step to improve biocompatibility and biodegradability properties to the surface of foreign materials. In addition, important biological functions can be integrated in such bio-inert materials. Therefore, the immobilization of biological compounds, such as proteins and peptides, is a straightforward method to modify their surfaces. In this chapter we discuss how different protein immobilization methods can influence cellular adhesion, proliferation and differentiation. Furthermore, we describe the chemistry behind the protein immmobilization step; specifically, we describe physisorption, covalent bonding, and ‘linker-free’ immobilization approaches. In each of these sections for protein immobilization, we have included a case study with pros and cons so the reader can follow these protocols and readily apply them in the laboratory.