The urgency of biological research, associated with the lack of experimentally solved structures, promotes an incredible leap in the accuracy and methods for protein structure prediction. Homology modeling is not only a pioneering solution for the gap between identified sequences and experimental structures but also the inspiration for developing new methods. Benefiting from the ongoing rise in the quantity of solved structures in Protein Data Bank (PDB) and development of conformation sampling techniques, the position of homology modeling is undeniable for protein structure prediction. In this chapter, the general concept and protocol are introduced to help understand the methodology of homology modeling. Moreover, the roles of homology modeling are discussed along with the application in various disciplines.