The design of large libraries of well-folded de novo proteins is a powerful approach toward the ultimate goal of producing proteins with novel structures and functions for use in industry or medicine. A method for library design that incorporates both rational design and combinatorial diversity relies on the "binary patterning" of polar and nonpolar amino acids. Binary patterning is based on the premise that the appropriate arrangement of polar and nonpolar residues can direct a polypeptide chain to fold into amphipathic elements of secondary structure that anneal together to form a desired tertiary structure. A designed binary pattern exploits the periodicities inherent in protein secondary structure, and allows the identity of the side chain at each polar and nonpolar position to be varied combinatorially. This chapter provides an overview of the considerations necessary to use binary patterning to design libraries of novel proteins.