This chapter discusses in vitro degradation behaviors of calcium phosphate particles, such as nano-crystalline hydroxyapatite (HAp) and ion-substituted HAp synthesized by the wet-chemical processing method, and how their microstructure affects their initial dissolution profiles and kinetics. The chapter reviews several in vitro evaluation techniques for biodegradability of calcium phosphate ceramics and several models representing dissolution profiles and kinetics. The chapter then discusses the relationship between the heterogeneous structure of nano-crystalline HAp and the initial dissolution behaviors in acidic buffer solution.