MicroRNAs (miRNAs), key posttranscriptional regulators of many biological processes, have been implicated in many diseases, including cancer. In a recent paper, Avraham and colleagues take a systems biology approach to determine whether and how miRNAs are involved in the regulation of oncogenic signaling networks downstream of epidermal growth factor (EGF). The authors showed that EGF stimulation orchestrated the transcription of both miRNAs and transcription factors. An early decrease in the abundance of a subset of miRNAs allowed for the induction of messenger RNAs of immediate early genes. Expression of this group of miRNAs was also decreased in tumors that showed deregulated signaling through the EGF receptor (EGFR) or the related receptor HER2. Their biological properties of redundancy, multiplicity, and rapid responsiveness make these small noncoding RNAs important regulators of cell signaling.