This symposium will discuss the basic biology of gene regulation by endogenous small RNAs, called microRNAs, which regulate a cell's response to developmental and environmental cues. Each microRNA regulates the expression of hundreds and possibly thousands of genes that bear partially complementary sequences, mostly in the 3'-untranslated region of the messenger RNA. This symposium will discuss microRNAs that regulate cell division, differentiation, survival, and immune responses. New methods to identify microRNA-regulated genes will be described. This symposium will also discuss how the RNA interference machinery, which is present in all cells, can be harnessed to inhibit disease-causing genes for therapy.