Small RNAs of 21-23 nucleotides are powerful regulators of gene expression and play essential roles in biological processes that include development, maintenance of genome stability, and viral adaptive defense mechanisms. Such small RNAs are simple in design yet rich in biology and have captivated the attention of biologists in many fields. This review discusses the potential roles of small RNAs in immune biology and speculates on their potential participation in lymphogenesis and antiviral mechanisms.