CD4 T cells are an integral part of adaptive immunity. microRNAs have been identified as fundamental regulators of post-transcriptional programs and to play roles in T lymphocytes' development, differentiation, and effector functions. To better understand the role of miRNAs in T cells and to identify potential therapeutic tools and targets, we have undertaken studies of miRNAs that modulate or are modulated by T-cell receptor signaling. We identified miR-181a as a key regulator of TCR signaling strength, and hence T-cell development, and the miR-17-92 cluster as an important player in CD4 T cells' response against antigens. These discoveries, coupled with work by other researchers, reveal the power and importance of miRNA-mediated regulation in T-cell responses and offer new insights into the burgeoning field of immunoregulation.