microRNAs (miRs) are small non-protein-coding RNAs, able to post-transcriptionally regulate many genes and exert pleiotropic effects. Alteration of miR levels in tissues and in the circulation has been associated with various pathological and regenerative conditions. In this regard, tissue engineering of cardiac and skeletal muscles is a fascinating context for harnessing the complexity of miR-based circuitries and signals. In this review, we will focus on miR-driven regulation of cardiac and skeletal myogenic routes in homeostatic and challenging states. Furthermore, we will survey the intriguing perspective of exosomal and circulating miRs as novel paracrine players, potentially useful for current and future approaches of regenerative medicine for the striated muscles.