Surface modification of electrodes and nanoparticles is the key to their efficiency and applicability in the biomedical field, including electrochemical biosensors, bioimaging, and implants. Traditionally, modified materials include self-assembled monolayers using alkanethiols or peptides, conductive polymers, and different types of nanoparticles. These materials should have biocompatible, antifouling properties, low toxicity, and high specific interaction with targets and be stable in contact with body fluids. At the same time, electrochemical-modified materials require important properties, such as conductivity, high electron transfer rate, large surface area, controlled surface roughness, surface functional groups, hydrophilic proprieties, and cost-effectiveness. This chapter discusses different immobilization strategies, including adsorption, covalent binding, cross-linking, entrapment, and affinity, followed by the main procedures. Self-assembled monolayers create a monomolecular layer with high organization on the top of solid surfaces. Recently redox-active and peptide monolayer are investigated to decrease nonspecific interactions and increase sensitivity. Conductive polymer coating significantly increases surface area allowing different immobilization strategies, including nanoparticle immobilization to increase electrochemical detection. Moreover, nanoparticles have been extensively investigated for biomedical applications, especially drug delivery. Therefore, surface-modified biomaterials have an incredible prospect for clinical diagnostics and therapy, but there is still a path to be followed to understand biocompatibility and toxicity, as well as improve the stability and specificity of modified biomaterials.