Crystallization is often a major bottleneck to macromolecular structure determination. This is particularly true for membrane proteins, which have hydrophobic surfaces that cannot readily form crystal contacts. Of the roughly 109,000 protein structures in the PDB, only about 539 represent unique membrane proteins, despite immense interest in membrane proteins from both a biological and therapeutic standpoint. Membrane protein crystallization has been facilitated by the development of new detergents, lipidic cubic phase methods, soluble protein chimeras, and non-covalent protein complexes. The design process of protein fusion constructs and non-covalent antibody fragments specific for each target membrane protein, however, is costly and time-consuming. An improved, more general method of membrane protein co-crystallization is needed. This dissertation details the development of two approaches for cost-effective non-covalent crystallization chaperones: (1) Engineered hypercrystallizable Fab antibody fragment with high affinity for EYMPME (EE epitope), which form complexes with EE-tagged soluble and membrane proteins. (2) Engineered monomeric streptavidin (mSA2) for complexation with biotinylated membrane proteins. Both methods are generalizable through insertion of a short epitope into a surface-exposed loop of a membrane protein by site directed mutagenesis. Crystallization trials of representative chaperone-membrane protein complexes and possible difficulties with the approach are discussed.