Anna M. Krichevsky and Galina Gabriely summarize the role of miR-21 in human disease, focusing on its regulation, oncogenic function, targets in human cancers, potential as a disease biomarker, and novel therapeutic target in oncology. miR-21 is one of the most studied miRNAs, along with let-7, miR-17–92 cluster, miR-155, and others. It is strongly up-regulated in various cancers, including gliomas, breast, colon, lung, pancreas, prostate, and stomach cancers, as well as in leukaemic cancers. miR-21 is also up-regulated in viral infections and virus-linked proliferative disorders. miR-21 is involved in cell cycle, apoptosis, and invasion in gliomas. It is a potential diagnostic and prognostic marker in cancer. miR-21 is regulated at multiple levels, including transcriptional and post-transcriptional regulation. miR-21 functions in cancer by targeting various genes, including PDCD4, RECK, and TPM1. miR-21 is involved in feedback regulation and may contribute to the self-sustained expression of miR-21 in cancer. miR-21 is also involved in TGF-β signaling and may regulate TGF-β pathway. miR-21 is a potential therapeutic target in oncology. miR-21 is a key molecule in the roadmap of carcinogenesis. Its expression may represent an adaptation to a hypoxic environment that favours cancer cell survival. miR-21 is a potential diagnostic and prognostic marker in cancer.Anna M. Krichevsky and Galina Gabriely summarize the role of miR-21 in human disease, focusing on its regulation, oncogenic function, targets in human cancers, potential as a disease biomarker, and novel therapeutic target in oncology. miR-21 is one of the most studied miRNAs, along with let-7, miR-17–92 cluster, miR-155, and others. It is strongly up-regulated in various cancers, including gliomas, breast, colon, lung, pancreas, prostate, and stomach cancers, as well as in leukaemic cancers. miR-21 is also up-regulated in viral infections and virus-linked proliferative disorders. miR-21 is involved in cell cycle, apoptosis, and invasion in gliomas. It is a potential diagnostic and prognostic marker in cancer. miR-21 is regulated at multiple levels, including transcriptional and post-transcriptional regulation. miR-21 functions in cancer by targeting various genes, including PDCD4, RECK, and TPM1. miR-21 is involved in feedback regulation and may contribute to the self-sustained expression of miR-21 in cancer. miR-21 is also involved in TGF-β signaling and may regulate TGF-β pathway. miR-21 is a potential therapeutic target in oncology. miR-21 is a key molecule in the roadmap of carcinogenesis. Its expression may represent an adaptation to a hypoxic environment that favours cancer cell survival. miR-21 is a potential diagnostic and prognostic marker in cancer.