The miR-17-92 cluster and its paralogs are known to act as oncogenes, promoting cell proliferation, suppressing apoptosis, and inducing tumor angiogenesis. Recent studies have revealed essential functions for these miRNAs not only in tumor formation but also in the normal development of the heart, lungs, and immune system. The miR-17-92 cluster is a polycistronic miRNA gene located on human chromosome 13, encoding six miRNAs that are highly conserved across vertebrates. These miRNAs are regulated by c-Myc and play a crucial role in controlling cellular life and death decisions, particularly through the E2F family of transcription factors. Overexpression or inhibition of these miRNAs can significantly affect cell-cycle progression and apoptosis. In cancer, the miR-17-92 cluster is often amplified and overexpressed, contributing to tumor growth and progression. However, loss-of-function studies in mice have shown that the miR-17-92 cluster is essential for the survival signal enabling progression from the pro-B to pre-B cell stage in B cell development. Additionally, overexpression of the miR-17-92 cluster in B and T cells leads to lymphoproliferative disease and autoimmunity. Future research will focus on elucidating the full network of targets regulated by these miRNAs and exploring their potential as therapeutic targets in cancer.The miR-17-92 cluster and its paralogs are known to act as oncogenes, promoting cell proliferation, suppressing apoptosis, and inducing tumor angiogenesis. Recent studies have revealed essential functions for these miRNAs not only in tumor formation but also in the normal development of the heart, lungs, and immune system. The miR-17-92 cluster is a polycistronic miRNA gene located on human chromosome 13, encoding six miRNAs that are highly conserved across vertebrates. These miRNAs are regulated by c-Myc and play a crucial role in controlling cellular life and death decisions, particularly through the E2F family of transcription factors. Overexpression or inhibition of these miRNAs can significantly affect cell-cycle progression and apoptosis. In cancer, the miR-17-92 cluster is often amplified and overexpressed, contributing to tumor growth and progression. However, loss-of-function studies in mice have shown that the miR-17-92 cluster is essential for the survival signal enabling progression from the pro-B to pre-B cell stage in B cell development. Additionally, overexpression of the miR-17-92 cluster in B and T cells leads to lymphoproliferative disease and autoimmunity. Future research will focus on elucidating the full network of targets regulated by these miRNAs and exploring their potential as therapeutic targets in cancer.