Numerous studies have implicated microRNAs (miRNAs) in cancer initiation and progression. In contrast, only recently has attention been focused on the pathway that generates these regulatory molecules. The identification of neoplasia-associated germline mutations in DICER1 has focused translational research on components of the miRNA processing pathway. Deciphering of the many links between miRNA processing perturbations and cancer will likely provide insights into mechanisms of cancer control.