Stem cells are a reserve of unique cells with self-renewal property. It differentiates into organ-specific cells to replace the dead tissues to restore the physiological functions. Based on their ability to differentiate into the whole organism, cells of all the three germ layers, cells of particular germline, or only the target cells, they are termed as totipotent, pluripotent, multipotent, or progenitor stem cells, respectively. Based on their source, they are classified as embryonic, nonembryonic, mesenchymal, perinatal, cancer, and induced pluripotent stem cells. The self-renewal and differentiation properties of stem cells made them an ideal therapeutic tool to treat diseases associated with tissue loss. Hence, the major neurological, musculoskeletal, skin, hematological, cardiac diseases, and diabetes mellitus once thought to be nontreatable has now gained the hope of remedy on the use of organ-specific stem cells. In addition, stem cells have been engineered for targeted enzyme prodrug delivery for the treatment of deep-seated tumors like glioblastoma. The major limitation in the use of stem cells for therapy is its propensity to form teratoma and distribution in nonpreferred sites. Hence, tailoring the stem cells to reach the desired niche and to restore the physiological functions is underway to develop a promising therapeutic modality for treating the various challenging diseases in the medical field. © 2020 Elsevier B.V., All rights reserved.