Stem cells can be defined as the cells that have the capacity to both self-renew and give rise to differentiated cells. Under the right conditions and signals, depending on their origin and bio-plasticity, stem cells can differentiate into multiple cell lineages and develop into various mature cells. Stem cell therapy is a fast-developing branch of medicine that includes the most innovative regenerative therapies for the restoration of cell and tissue function in individuals with severe diseases. Stem cell research has resulted in the emergence of cell-based therapies for disorders that are resistant to conventional drugs and therapies, and they are considered under the category of an Advanced Therapeutic Medicinal Product (ATMP). The FDA and the European Medicines Agency (EMA) devised a new strategy in 2017 with the aim of unifying the standards for development of ATMPs such that it is easy to exchange information at the international level. In this review, we discuss the evolution of mesenchymal stem cell-based therapy as an ATMP in the global and Indian scenarios, along with the guidelines governing their usage and clinical application of these therapeutics.