Mucoadhesive drug delivery systems (MDDS) are a new concept that has been proposed as an alternative to traditional means of drug delivery with many benefits, including greater bioavailability, an extended residence time, and local delivery to definite mucosal surfaces. These systems are premised on the fact that some polymers could be attached to the mucosal surfaces which allowed drugs to be released continuously and enhance therapy. Mucoadhesive mechanisms are largely due to the interaction between the polymer and the mucin layer of mucosal surfaces with major theories of wetting, diffusion, electronic, adsorption, fracture, and mechanical interlocking. MDDS have been extensively investigated in many different routes of administration among them being oral, nasal, ocular, vaginal, and gastrointestinal. They have demonstrated high potentiality in the delivery of small molecules and biologics including proteins, peptides, and vaccines. In clinical practice, better patient adherence, less frequent dosing, and the management of chronic disease like pain, hypertension and infections has been demonstrated. Although these benefits are evident, issues like mucus turnover, polymer toxicity, and irritation should be overcome in order to maximize the performance of MDDS. The new trends, including the application of stimuli-responsive polymers, which are nanocarriers, 3D printing technology and others, are leading to the more innovative and customized mucoadhesive therapies, which are likely to make the drug delivery system improved further.