Flexible pressure sensors are attracting great interest from researchers and are widely applied in various new electronic equipment because of their distinct characteristics with high flexibility, high sensitivity, and light weight; examples include electronic skin (E-skin) and wearable flexible sensing devices. This review summarizes the research progress of flexible pressure sensors, including three kinds of transduction mechanisms and their respective research developments, and applications in the fields of E-skin and wearable devices. Furthermore, the challenges and development trends of E-skin and wearable flexible sensors are also briefly discussed. Challenges of developing high extensibility, high sensitivity, and flexible multi-function equipment still exist at present. Exploring new sensing mechanisms, seeking new functional materials, and developing novel integration technology of flexible devices will be the key directions in the sensors field in future.