Hydroxyapatite (HAP) is a green catalyst that has a wide range of applications in catalysis due to its high flexibility and multifunctionality. These properties allow HAP to accommodate a large number of catalyst modifications that can selectively improve the catalytic performance in target reactions. To date, many studies have been conducted to elucidate the effect of HAP modification on the catalytic activities for various reactions. However, systematic design strategies for HAP catalysts are not established yet due to an incomplete understanding of underlying structure–activity relationships. In this review, tuning methods of HAP for improving the catalytic performance are discussed: 1) ionic composition change, 2) morphology control, 3) incorporation of other metal species, and 4) catalytic support engineering. Detailed mechanisms and effects of structural modulations on the catalytic performances for attaining the design insights of HAP catalysts are investigated. In addition, computational studies to understand catalytic reactions on HAP materials are also introduced. Finally, important areas for future research are highlighted.