Microsponges delivery system (MDS) is highly porous, cross-linked based polymeric systems, that activates in the presence of temperature, rubbing and pH. MDS offers wide range of advantage, like controlled drug release, site-specific action, stable over a broad range of pH, poor irritation, cost effective, improved patient compliance. They can be transformed into various dosage forms like creams, gels, and lotions. MDS based system are suitable for treatment of topical disorders like acne, psoriasis, dandruff, eczema, scleroderma, hair loss, skin cancer, and other dreadful diseases. MDS application for drug delivery is not limited to topical drug delivery but also explored for oral, parenteral and pulmonary drug delivery. Microsponges were studied for colon targeting of drugs and genes. Additionally, MDS has wide application for sunscreen, cosmetics, and over the counter (OTC) products. Furthermore, MDS does not actuate any irritation, genotoxicity, immunogenicity or cytotoxicity. Therefore, this review extensively highlights about microsponges, their advantages, key factors affecting the micro-sponges’ characteristics, the therapeutic application of microsponges in topical disorders, cancer, as cosmetics, recent advances in MDS and addresses the associated challenges.