A mucoadhesive drug delivery system (MDDS) has been a smart approach to the delivery of drugs at the target site. In MDDS mucus membrane and type of polymer plays an important role in the mucoadhesion phenomenon. To explain the mechanism behind mucoadhesion, various theories have been proposed such as electronic, adsorption, wetting, diffusion, and fracture theory. MDDS has been beneficial to some special patients, preferably pediatric and geriatric. Several challenges such as taste masking, dose determination, dosage form spitting, target delivery, the bioavailability of the drug, adverse drug reaction, toxicity, etc. are faced while developing any delivery system for these special patient populations. Keeping these challenges in mind several researchers have attempted to design and formulate MDDS according to their convenience. The current review focuses on a basic overview of mucoadhesion, various theories of mucoadhesion, and mucoadhesive polymers. The later part of the review focuses on the MDDS for pediatric and geriatric patients with their significance. Various patented formulations and clinical trials going on for these populations have also been discussed.