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The systemic administration of drugs to treat bone diseases is often associated with poor uptake of the drug in the targeted tissue, potential systemic toxicity and suboptimal efficacy. In order to overcome these limitations, many micro- and nano-sized drug carriers have been developed for the treatment of bone pathologies that exhibit specific affinity for bone. Drug carriers can be functionalized with bone mineral seekers (BMS), creating a targeted drug delivery system (DDS) which is able to bind to bone and release therapeutics directly at the site of interest. This class of advanced DDS is of tremendous interest due to their strong affinity to bone, with great expectation to treat life-threatening bone disorders such as osteomyelitis, osteosarcoma or even osteoporosis. In this review, we first explain the mechanisms behind the affinity of several well-known BMS to bone, and then we present several effective approaches allowing the incorporation BMS into advanced DDS. Finally, we report the therapeutic applications of BMS based DDS under development or already established. Understanding the mechanisms behind the biological activity of recently developed BMS and their integration into advanced therapeutic delivery systems are essential prerequisites for further development of bone-targeting therapies with optimal efficacy.