There has been much recent activity in the research area of nanoparticles and nanocrystalline materials, in many fields of science and technology. This is due to their outstanding and unique physical, mechanical, chemical and biological characteristics. Recent developments in biomineralization have demonstrated that nano-sized particles play an important role in the formation of the hard tissues of animals. It is well established that the basic inorganic building blocks of bones and teeth of mammals are nano-sized and nanocrystalline calcium orthophosphates (in the form of apatites) of a biological origin. In mammals, tens to hundreds of nanocrystals of biological apatite are found to combine into self-assembled structures under the control of bio-organic matrixes. It was also confirmed experimentally that the structure of both dental enamel and bones could be mimicked by an oriented aggregation of nano-sized calcium orthophosphates, determined by the biomolecules. The application and prospective use of nano-sized and nanocrystalline calcium orthophosphates for clinical repair of damaged bones and teeth are also known. For example, a greater viability and a better proliferation of various cells were detected on smaller crystals of calcium orthophosphates. Furthermore, studies revealed that the differentiation of various cells was promoted by nano-sized calcium orthophosphates. Thus, the nano-sized and nanocrystalline forms of calcium orthophosphates have the potential to revolutionize the field of hard tissue engineering, in areas ranging from bone repair and augmentation to controlled drug delivery devices. This paper reviews the current state of knowledge and recent developments of various nano-sized and nanocrystalline calcium orthophosphates, covering topics from the synthesis and characterization to biomedical and clinical applications. This review also provides possible directions of future research and development.