Nanofi brous scaffolds which mimic the structural features of a natural extracellular matrix (ECM) can be appealing scaffold candidates for tissue engineering as they provide similar physical cues to the native environment of the targeted tissue to regenerate. This chapter discusses different strategies to fabricate nanofi brous scaffolds for tissue engineering. We fi rst describe three major methods for nanofi brous scaffold fabrication: molecular self-assembly, phase separation, and electrospinning. Then, approaches for surface modifi cation of nanofi brous scaffolds including blending and coating, plasma treatment, wet chemical methods, and surface graft polymerization are presented. Finally, applications of nanofi brous scaffolds in tissue engineering are introduced.