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The aim of this study is to review the advantages of mucoadhesive microspheres, mechanisms, and theories involved in mucoadhesion, factors that affect the mucoadhesion and polymers in mucoadhesive drug delivery systems. Gastroretentive drug delivery systems are those which are retained in the stomach for a longer period of time and thereby improve the bioavailability of drugs. Mucoadhesion is a topic of current interest in the design of drug delivery systems. Mucoadhesion is currently explained by six theories: electronic, adsorption, wetting, mechanical, diffusion, and fracture. Microspheres constitute an important part of these particulate drug delivery systems by virtue of their small size and efficient carrier capacity, but coupling of bioadhesive properties to these microspheres has additional advantages such as prolong residence time of the dosage form at the site of absorption and intimate contact of the dosage form with the underline absorption surface contributed to improved therapeutic performance of the drug or improved bioavailability of drug, reduced dosing frequency, and improved patience compliance.