Generating artificial protein assemblies with complex shapes requires a method of connecting protein components withstable and predictable structures. Because they have uniform structures, alpha helices can provide an excellent linker forconnecting proteins with predictable structures. However, except for a few exceptional cases, early attempts to ligate twoproteins by fusion of terminal alpha helices were not successful. In order to solve this problem, several new methods havebeen developed in recent years. In the chemical cross-linker method, the linker helix is stabilized by a chemical cross-linkerthat can force an alpha helical geometry by fixing the distance between two cysteine residues. In the shared-helix method,the linker helix is generated by overlapping pairs of alpha helices by 1~2 turns using a molecular modeling program. Theamino acid sequence at the overlapped site is chosen from the two natural sequences that would stabilize the alphahelical linker. These two helix fusion methods are expected to be useful in structural biology because they can enhancethe crystallization property of challenging target proteins by providing a rigid and crystallizable surface. They also can beused to produce artificial protein complexes by connecting the target protein to a large backbone protein. The resultingprotein complex effectively increases the size of the target protein for cryo-electron microscopy study. In this review, wesummarize recent progress of the helix fusion methods and their application to structural study of challenging proteins.