Pancreatic β-cells located within the islets of Langerhans play a central role in metabolic control. The main function of these cells is to produce and secrete insulin in response to a rise in circulating levels of glucose and other nutrients. The release of insufficient insulin to cover the organism needs results in chronic hyperglycemia and diabetes development. β-cells insure a highly specialized task and to efficiently accomplish their function they need to express a specific set of genes. MicroRNAs (miRNAs) are small noncoding RNAs and key regulators of gene expression. Indeed, by partially pairing to specific sequences in the 3' untranslated regions of target mRNAs, each of them can control the translation of hundreds of transcripts. In this review, we focus on few key miRNAs controlling islet function and discuss: their differential expression in Type 2 diabetes (T2D), their regulation by genetic and environmental factors, and their therapeutic potential. Genetic and epigenetic changes or prolonged exposure to hyperglycemia and/or hyperlipidemia can affect the β-cell miRNA expression profile, resulting in impaired β-cell function and survival leading to the development of T2D. Experimental approaches permitting to correct the level of misexpressed miRNAs have been shown to prevent or treat T2D in animal models, suggesting that these small RNAs may become interesting therapeutic targets. However, translation of these experimental findings to the clinics will necessitate the development of innovative strategies allowing safe and specific delivery of compounds modulating the level of the relevant miRNAs to the β-cells.