A unique class of molecular host frameworks based on hydrogen-bonded sheets of guanidinium ions and sulfonate moieties of organodisulfonate “pillars” will be described that afford well-defined inclusion cavities with sizes, shapes and physicochemical characteristics that can be tuned systematically through control of the pillar structure.  The structural robustness of the hydrogen-bonded sheets leads to persistent lamellar architectures that enable structure prediction, including crystal symmetry and metrics.  The inclusion cavities can be occupied by wide variety of functional guest molecules that also serve as templates for the assembly of the frameworks.  The persistence of the lamellar architecture can be attributed to the conformational flexibility of the hydrogen-bonded sheets and the organodisulfonate pillars.  This flexibility, as well as a topological isomerism that produces numerous lamellar architectures, permits the host frameworks to conform to differently sized and shaped guest molecules, thereby providing a mechanism for achieving the cohesive energy that drives the formation of these materials.  The persistence of the guanidinium-sulfonate hydrogen-bonded sheets also enables the formation of porous tubular architectures having the same supramolecular hydrogen-bonding connectivity as the lamellar phases.  The lamellar and tubular structures are reminiscent of lamellar and hexagonal surfactant microstructures with respect to their structural characteristics and persistence.  The predictable character of these frameworks has enabled rational design of polar crystals with second harmonic generation activity, controlled organization of organic guest molecules in two-dimensional layers, and separation of isomeric organic compounds.