Extracellular RNAs consist of coding and non-coding transcripts released from all cell types, which are involved in multiple cellular processes, predominantly through regulation of gene expression. Recent advances have helped us better understand the functions of these molecules, particularly microRNAs (miRNAs). Numerous pre-clinical and human studies have demonstrated that miRNAs are dysregulated in cancer and contribute to tumorigenesis and metastasis. miRNA profiling has extensively been evaluated as a non-invasive method for cancer diagnosis, prognostication, and assessment of response to cancer therapies. Broader applications for miRNAs in these settings are currently under active development. Investigators have also moved miRNAs into the realm of cancer therapy. miRNA antagonists targeting miRNAs that silence tumor suppressor genes have shown promising pre-clinical activity. Alternatively, miRNA mimics that silence oncogenes are also under active investigation. These miRNA-based cancer therapies are in early development, but represent novel strategies for clinical management of human cancer.