The Drosophila genome is estimated to encode 152 microRNAs. This equates to about 1% of all genes. To understand their functions we have taken a systematic approach to producing microRNA mutants by targeted homologous recombination. Our approach combines conventional genetic analysis, to understand the biological process affected by the microRNA, with computational and biochemical tools to identify the target genes that microRNAs regulate. Many microRNA genes in the fly are expressed in the CNS, and evidence is emerging to link their functions to maintenance of neuronal cells and to neuronal function. Some microRNA mutants cause neurodegeneration, and others appear to cause behavioral defects. By identifying their targets we hope to understand the basic cellular processes that can cause neurodegeneration in the fly as a means to identify new links to disease. I will present a progress report on the genome wide survey of microRNA mutant phenotypes and highlight examples where we can assign specific neuronal functions to miRNAs.