Cancer remains a worldwide epidemic. An improved understanding of the underlying molecular mechanisms and development of effective targeted therapies are still required for many deadly cancers. The discovery of microRNAs (miRNAs or miRs) nearly 20 years ago introduced a new layer of complexity to gene regulation, but it also afforded us the opportunity to further our understanding of the molecular pathogenesis of cancers. Dysregulation of miRNAs is fundamental to the pathogenesis of many cancers based on their involvement in basic cellular functions. In addition, these previously underrecognized, noncoding RNAs have the capacity to target tens to hundreds of genes simultaneously. Thus, they are attractive candidates as prognostic biomarkers and therapeutic targets in cancer. However, several challenges remain in translating our current understanding of miRNAs to clinical therapies. Herein, we provide a review of the current knowledge of miRNAs in both solid and hematological malignancies with a focus on their potential application as therapeutic targets in cancer.