Mucoadhesive microspheres are one of the most promising novel techniques for drug delivery. Mucoadhesive systems offer a sustained drug release method, thus enhancing drug absorption in a site-specific manner. Microspheres have very small sizes and provide efficient carrier capacities. Mucoadhesive systems therefore play a vital role in drug delivery systems. Mucoadhesion is a two-step procedure, and its mechanism can be explained by combining theories of wetting, mechanical interlocking, electronic transfer, adsorption, fracture, and diffusion interpenetration, as deemed suitable. Mucoadhesive microspheres offer added advantages of reliability, safety, specificity, prolonged action, delayed release, and enhanced activity along with a very few disadvantages. These systems can be prepared by emulsion cross-linking, single emulsion, ionotropic gelation, phase inversion, spray drying, solvent removal, and hot melt methods. The resulting microspheres are characterized using a number of parameters such as size, surface, efficiencies, and release studies. Mucoadhesive microspheres have been developed for oral, buccal, nasal, ocular, rectal, and vaginal applications with systemic as well as local effects. They give a chance to deliver the drugs which were not possible to administer by oral route. This review article gives an overview of mucoadhesive microspheres, their pros and cons, preparation methods, characterization, application, and recent developments.