Outside the confines and well-established domain of organic chemistry, the systematic building of large macromolecular arrangements based on non-carbon elements represents a significant and exciting challenge. Our aim in the past two decades has been to develop robust synthetic methods to construct new types of main group architectures in a methodical way, principles of design that parallel those used in the organic arena. This concept article addresses the fundamental thermodynamic and kinetic problems involved in the design and synthesis of main group macrocycles and looks to future developments of macromolecules in this area, as well as new applications in coordination chemistry.