Spatial distribution perception has become an important trend for flexible pressure sensors, which endows wearable health devices, bionic robots, and human–machine interactive interfaces (HMI) with more precise tactile perception capabilities. Flexible pressure sensor arrays can monitor and extract abundant health information to assist in medical detection and diagnosis. Bionic robots and HMI with higher tactile perception abilities will maximize the freedom of human hands. Flexible arrays based on piezoresistive mechanisms have been extensively researched due to the high performance of pressure-sensing properties and simple readout principles. This review summarizes multiple considerations in the design of flexible piezoresistive arrays and recent advances in their development. First, frequently used piezoresistive materials and microstructures are introduced in which various strategies to improve sensor performance are presented. Second, pressure sensor arrays with spatial distribution perception capability are discussed emphatically. Crosstalk is a particular concern for sensor arrays, where mechanical and electrical sources of crosstalk issues and the corresponding solutions are highlighted. Third, several processing methods are also introduced, classified as printing, field-assisted and laser-assisted fabrication. Next, the representative application works of flexible piezoresistive arrays are provided, including human-interactive systems, healthcare devices, and some other scenarios. Finally, outlooks on the development of piezoresistive arrays are given.