Poor osseointegration and bacterial infection are major causes of orthopedic implant failure. Both problems arise from passive unspecific protein coating that may not optimally support adhesion of osteoblastic cells and which enable bacterial adhesion that subsequently results in biofilm formation. This review addresses emerging concepts of preventing unspecific protein adsorption and biofilm formation by organic coating systems. We especially focus on recent concepts that additionally allow functionalization for preferential cell adhesion using cell adhesion mediating small peptide sequences that do not induce bacterial adherence. One promising approach that is presented and discussed within this context is the use of NCO-sP(EO-stat-PO).