It is currently well recognized that microRNA deregulation is a hallmark of human cancer, and an aberrant expression of these tiny regulatory RNA molecules in several cell types is not just a random association, but it also plays a causal role in different steps of the tumorigenic process, from the initiation and development to progression toward the acquisition of a metastatic phenotype. Different regulatory mechanisms can control microRNA expression at a genetic or epigenetic level as well as involve the biogenesis machinery or the recruitment of specific transcription factors. The tumorigenic process implies a substantial alteration of these mechanisms, thus disrupting the equilibrium within the cell and leading to a global change in microRNA expression, with loss of oncosuppressor microRNAs and overexpression of oncomiRNAs. We review the main mechanisms regulating microRNAs and the consequences of their aberrant expression in cancer, with a glance at the possible implications at a clinical point of view.