In record time, microRNAs (miRNAs) have acquired the respected stature of important natural regulators of global gene expression. Multiple studies have demonstrated that a large number of miRNAs are under the control of various metabolic stimuli, including nutrients, hormones, and cytokines. Conversely, it is now well recognized that miRNAs control metabolism, thereby generating a bidirectional functional link, which perturbs energy homeostasis in case of disconnection in the miRNA-metabolism interplay. A challenging road lies ahead for defining the role of miRNAs in the pathogenesis of diseases such as diabetes and for establishing their usefulness as new medications and clinically reliable biomarkers.