Hydrogen-bonded frameworks (HBFs) have been studied for decades owing to their fascinating and diverse architectures, always with an eye toward the role of hydrogen bonding in their design as well as their utility in various applications. This review addresses recent advances in HBFs that illustrate their versatility and utility stemming from their unique attributes compared with other classes of molecular frameworks. Guanidinium organosulfonate hydrogen-bonded frameworks, pioneered in our lab and one of the most extensive and versatile collections of HBFs, are used to illustrate molecular design concepts and the principle of architectural isomerism that expands access to a greater structural landscape. Recognizing the growing role of computation in materials design, from ab initio methods to machine learning, this review also touches on their emerging use in the design and synthesis of HBFs. The growth of the HBF arsenal promises continuing innovations, with applications ranging from electronic materials and chemical separations to gas adsorption and catalysis.