MicroRNAs are endogenous, regulatory, noncoding small RNAs shown to play a key role in controlling gene expression, mainly at the posttranscriptional level. Several lines of evidence highlighted the importance of selected microRNAs as essential actors of cancer initiation events, tumor progression towards malignancy, and ultimately metastasis. By acting as either prometastatic or antimetastatic factors, microRNAs may represent novel targets or tools to withstand cancer progression. This chapter summarizes the available strategies to manipulate the expression of metastasis-related microRNAs, either by mimicking or inhibiting them, in cell systems and in vivo models. In addition, we provide a broad overview of conceptual and technological issues that need to be addressed before microRNAs might be exploited in the clinical setting for the prevention and treatment of the metastatic disease.