Phosphate ores, which are regarded as critical mineral resources, play an important role in various industrial fields. Apatite is the main source of phosphate mineral resources and must be concentrated before it is processed into industrial products. Flotation is the most commonly employed method for apatite concentration. However, as the proportion of fine apatite increases, the challenge of separating it from gangue minerals intensifies, due to the resemblance in surface characteristics between apatite and gangue. Interfacial regulation during flotation is fundamental to the process, including the regulation of the mineral/water interface wettability by flotation reagents (collectors and modifiers), the control of interactions between mineral particles, and the regulation of interactions between mineral particles and bubbles. This article introduces the surface characteristics of apatite and its main gangue minerals. It discusses innovative work on flotation reagents (primarily collectors and depressants) and their action mechanisms on mineral surfaces. It reviews the current development of theories on the regulation of interactions between interparticles and between particles and bubbles. Finally, the study outlook the future research on interfacial regulation in apatite flotation. This study is intended to offer references for the continued advancement of apatite flotation.