Stretchable and flexible piezoresistive sensors (SFPSs) can detect mechanical stimuli in terms of electrical response and provide adaptability to use with complex surfaces, whether stationary or moving. Its stretchable and flexible nature makes it ideal for detecting large strains, localized pressure, bending, and twisting. SFPSs can detect pressure and strain in a broad range. SFPSs have ease of manufacturing, high sensitivity, better durability, easy processing, and economic development. These qualities of SFPSs can open a wide range of application possibilities, such as healthcare, human motion detection, a safe environment to interact with robots, automation, and soft robotics. The discussion in this article starts from the sensing mechanism, design development over the years, a variety of materials used for substrates and to provide conductivity to the sensors, fabrication processes explored and developed, enhancement in the performance characteristics, to have future directions. Over the last decades, exponential development has occurred in SFPSs systems based on design mechanisms, materials used, and fabrication techniques, even though several technological and design challenges remain undetermined and bear decisive interdisciplinary intervention to address them.