Hybrid materials based on layered double hydroxides (LDHs) exhibit great potential in diverse fields such as health care, polymer composites, environment, catalysis, and energy generation. Indeed, the compositional flexibility and the scalability of LDH structures, their low cost, and their ease of synthesis have made hybrid LDHs extremely attractive for constructing smart and high-performance multifunctional materials. This review provides a comprehensive and critical overview of the current research on multifunctional hybrid LDHs. Organic–inorganic hybrid LDHs, intercalated and surface-immobilized structures, are both specifically addressed. The new trends and strategies for hybrid LDH synthesis are first described, and then the potential of the latest hybrid LDHs, polymer LDH nanocomposites, and LDH bio-nanocomposites are presented. Significant achievements published from ≈2010, including authors' results, which employ hybrid LDH assemblies in materials science, medicine, polymer nanocomposites, cement chemistry, and environmental technologies, are specifically addressed. It is concluded with remarks on present challenges and future prospects.