There are various approaches for the delivery of therapeutic substance to the target site in a controlled release fashion. One such approach is using microspheres as carriers for drugs or active pharmaceutical compound. However, the success of this drug delivery system is limited due to their short residence time at the site of absorption. Mucoadhesive microspheres can be tailored to adhere to any mucosal tissue including those found in stomach, thus offering the possibilities of localized as well as systemic controlled release of drugs. This article presents the  advantages of Mucoadhesive microsphere, mechanism, theories involved in mucoadhesion, factor that affect the mucoadhesion, polymer in Mucoadhesive drug delivery system, methodology of preparation of Mucoadhesive microsphere, method of evaluation and their applications in drug delivery. Mucoadhesive drug delivery systems promises several advantages that arise from localization at a given target site, prolonged residence time at the site of drug absorption and an intensified contact with the mucosa increasing the drug concentration gradient.