Abstract With the pursuit of new cancer therapies and more effective treatment to diseases in the last decades, nanotechnology has been an important ally for healthcare professionals and patients in critical clinical conditions. Nanomaterials offer an alternative way to deliver toxic chemotherapeutic drugs to specific biological tissues, specific cells or specific microbial beings, resulting in avoidance of strong side effects or resilience to effective drugs. Among these materials, stands out the hydroxyapatite nanoparticles, a ceramic class of calcium phosphates that present chemical and structural similarities with the mineral phase of the human skeleton’s bone matrix, resulting in important biological features, such as biocompatibility, osteoconductive, osteoinduction and osteoaffinity, which led to a lot of scientific researches to apply these nanoparticles for bone diseases diagnosis and therapeutics. Due to the hydroxyapatite biological activities and due to the possibility to promote chemical and physical modifications in these nanoparticles, they can interact with biological cells or microorganisms in different ways, resulting in multiple potentialities to be explored such as apoptosis induction to cancerous cells, osteogenesis promotion, cellular proliferation, angiogenesis and tissue recovery, in addition to promote cell adhesion and cell uptake. Furthermore, chemical and physical modifications, such as surface functionalization, dopant inclusions and radiolabeling process, allow scientists to track the particle activities in biological environments. In the last decades of scientific productions, the literature brings together important data on how hydroxyapatite nanoparticles interact with biological tissues and such data are crucial for the development of more effective therapeutic and diagnostic agents. In the present review, we intend to compile scholarly information to explore the biological relations of nanosized hydroxyapatite with the human cellular environment and the feasible modifications that may improve the theragnostic efficacy of these molecules.