Genomic evidence reveals that gene expression in humans is precisely controlled in cellular, tissue-type, temporal, and condition-specific manners. Completely understanding the regulatory mechanisms of gene expression is therefore one of the most important issues in genomic medicine. Surprisingly, recent analyses of the human and animal genomes have demonstrated that the majority of RNA transcripts are relatively small, non-coding RNAs (sncRNAs), rather than large, protein coding message RNAs (mRNAs). Moreover, these sncRNAs may represent a novel important layer of regulation for gene expression. The most important breakthrough in this new area is the discovery of microRNAs (miRNAs). miRNAs comprise a novel class of endogenous, small, non-coding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. As a group, miRNAs may directly regulate about 30% of the genes in the human genome. In keeping with the nomenclature of RNomics, which is to study sncRNAs on the genomic scale, microRNomics is coined here to describe a novel sub-discipline of genomics that studies the identification, expression, biogenesis, structure, regulation of expression, targets and biological functions of miRNAs on the genomic scale. A growing body of exciting evidence suggests that miRNAs are important regulators of cell differentiation, proliferation/growth, mobility and apoptosis. These miRNAs therefore play important roles in development and physiology. Consequently, dysregulation of miRNA function may lead to human diseases such as cancer, cardiovascular disease, liver disease, immune dysfunction and metabolic disorders. microRNomics may be a newly emerging approach for human disease biology.