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MicroRNAs are small non-coding RNAs which regulate gene expression and silence a wide set of target genes. Aberrant miRNA expression has been described in cancer cells and is at least in part responsible of cancer initiation, development and progression. Due to their role, miRNAs have emerged as therapeutic targets or molecules suitable at the therapeutic level as well as markers of the response to chemo/radio/targeted therapy. Restoration or repression of miRNAs expression and activity shows high potential in managing cancer, and many studies on pre-clinical models have demonstrated the feasibility and efficacy of miRNA-based therapy. However, despite the exciting potential, some limitations, due to the degree of delivery and biodistribution or to possible side effects, need to be taken into consideration and solved in order to accomplish transition to clinical application. In this review we report and discuss the role of miRNAs in cancer, focusing on their use as therapeutic agents and their involvement in modulating/affecting the response to chemo/radio/targeted therapy in some of the most frequent solid tumors.