Bioceramics are the materials which can enhance the quality and longevity of human life. Hydroxyapatite (HAP) is a readily considered bioceramic material for artificial bone substitution in biomedical field due to its compositional resemblance to the bone mineral and very good biocompatiblity. Recently, HAP has attracted significant interest in drug delivery and bone tissue engineering applications. The human cortical bone consists of biological HAP which is found within collagen as nanodimensional crystalline aggregates. There has been enormous effort in developing bioactive synthetic ceramics that could closely mimic the fine and complex structure of human bone. Though HAP is highly biocompatible and bioactive, it possesses poor mechanical properties. In order to overcome this drawback, attempts are made toward the synthesis of mineralized HAP. Several methodologies have been investigated and developed for the synthesis of pure and substituted HAP. Modern research deals with novel HAP nanostructure formulations with properties closer to those of living bone, aiming at improved and more effective biomedical applications. This chapter presents the facile and cost-effective synthesis methods of pure and substituted HAP nanoparticles such as sol-gel approach, hydrothermal techniques, etc., toward effective biomedical applications.