Surface immobilization with active functional molecules (AFMs) on a nano-scale is a main field in the current biomaterial research. The functionalization of a vast number of substances and molecules, ranging from inorganic calcium phosphates, peptides and proteins, has been investigated throughout recent decades. However, in vitro and in vivo results are heterogeneous. This may be attributed partially to the limits of the applied immobilization methods. Therefore, this paper highlights the advantages and limitations of the currently applied methods for the biological nano-functionalization of titanium-based biomaterial surfaces. The second part describes a newer immobilization system, using the nanomechanical fixation of at least partially single-stranded nucleic acids (NAs) into an anodic titanium oxide layer as an immobilization principle and their hybridization ability for the functionalization of the surface with active functional molecules conjugated to the respective complementary NA strands.