Bone metastasis is a common and devastating complication of late-stage breast cancer. Metastatic bone disease arises as a result of perturbed bone remodeling due to various interactions between cancer cells and the bone microenvironment. Besides secreted regulators this complex system is governed by interconnected signaling pathways, transcription factors, genetic determinants and epigenetic cues including non-coding RNAs. Recent evidence demonstrates that many key drivers of bone metastasis are regulated by microRNAs (miRNAs), small non-coding RNAs that post-transcriptionally inhibit protein abundance and control several physiological and pathological processes including bone remodeling and cancer progression. In a physiological context in bone, miRNAs regulate osteoblast-mediated bone formation and osteoclast-related bone resorption, thereby contributing to the maintenance of bone homeostasis. Under pathological conditions, an aberrant miRNA signaling network contributes to the onset and progression of diseases such as bone metastasis. Interestingly, miRNAs important for bone homeostasis are often dysregulated in bone metastatic cancer cells. Furthermore, miRNAs can be secreted from cells to circulation. As a consequence, miRNAs have clinical potential as non-invasive disease-specific biomarkers. In a therapeutic context, miRNA delivery or antagonism has been reported to modulate several diseases under experimental and pre-clinical conditions thereby emerging as novel therapeutic tools. This presentation will focus on the role of miRNAs as important molecular regulators of transcription factors and signaling pathways driving bone metastasis. Furthermore, the possible novel role of secreted miRNAs in cell–cell communication in the tumor and bone environment, as well as the clinical potential of using miRNAs as diagnostic tools and therapeutic targets to treat metastatic bone disease will be discussed.