A growing body of evidence suggests that certain microRNAs (miRNAs) play causal roles in tumorigenesis by regulating genes that control cellular processes such as cell cycle, apoptosis, and differentiation. Lately, work in our laboratory has revealed that a specific miRNA can cause cancer cells to invade and metastasize. Here we review recent progress made in several laboratories concerning the roles played by miRNAs in cancer pathogenesis and metastatic spread, with the focus on the pro-metastatic microRNA, miR-10b, and discuss the future directions and possibilities for clinical applications.