Standard therapeutic approaches of cytotoxics and radiation in cancer are not only highly toxic, but also of limited efficacy in treatment of a significant number of cancer patients. The molecular analysis of the cancer genomes have shown a remarkable complexity and pointed to key genomic and epigenomic alterations in cancer. These discoveries are paving the way for targeted therapy approaches. However, although there are a large number of potential targets, only a few can regulate key cellular functions and intersect multiple signaling networks. The Aurora kinase family members (A, B, and C) are a collection of highly related and conserved serine-threonine kinases that fulfill these criteria, being key regulators of mitosis and multiple signaling pathways. Alterations in Aurora kinase signaling are associated with mitotic errors and have been closely linked to chromosomal aneuploidy in cancer cells. Several studies have shown amplification and/or overexpression of Aurora kinase A and B in hematologic malignancies and solid tumors. Over the past several years, Aurora kinases have become attractive targets. Several ongoing clinical trials and bench-based research are assessing the unique therapeutic potential of Aurora-based targeted therapy.