Small RNA is a variable and abundant type of non-coding RNAs in brain. The function of these RNAs is mainly unknown. A specific class of small RNA, microRNA, is dynamically regulated in neurogenesis and in embryo brain development. The genes for synaptic formation and some mental retardation disorders are putative targets for microRNA predicted by computational algorithms. The molecular pathways for mental development, common forms of autisms, schizophrenia, and affective disorders have yet to be elucidated. The hypothesis proposed here is that small regulatory RNAs, specifically microRNAs, play a role in human brain development and pathogenesis of brain disorders, especially of neurodevelopmental conditions. Pilot tests using comprehensive arrays of microRNAs demonstrate that microRNAs derived from postmortem human brains are applicable for microRNA expression profiling. The abundant expression of many regulatory small RNAs in human brain implies their biological role that must be tested by functional assays in neurons and by genetic and comparative expression profiling.