Acoustics has high variety of applications ranging from structural-health monitoring, sonar, and biological applications to sensors. The acoustic domain employs pressure waves for detection and provides better performance for sensing applications that require interactions with mechanical signals. High-performance sensing is possible by using acoustic biosensors in biological applications since most of the biological signals are in mechanical domain, in which the sensing mechanism directly interacts with them. In this chapter, the physics for different acoustic modes are introduced and their specific applications are mentioned, as well as sensing principles and operating mechanisms are presented. Also, the structural perspectives for acoustic biosensors are given and the fabrication techniques and materials are described. In this chapter, the biochemical principles behind the sensing are introduced and the layers and surfaces interacting with biomolecules are discussed. Some of the commercially available acoustic biosensors are presented and a short discussion of future perspectives is given.