A practical chemical sensor has been demanded for decades in various fields, such as medicine, security, and environmental science. Recently, the comprehensive optimization of materials science, mechanics, crystallography, and electronics led us to an effective sensing platform; a piezoresistive nanomechanical membrane-type surface stress sensor (MSS). The unique structure of the MSS makes it possible to fulfill the requirements for a practical sensor; high sensitivity, high mechanical/thermal/electrical stability, high reproducibility, simple operation, small size, and compatibility with mass production. Since MSS can detect almost any kind of molecule ranging from gaseous to biological species in various conditions including ambient air or opaque liquids such as blood, MSS is expected to realize a practical chemical sensor for real life applications; for example, private real-time blood test, landmine detection, pollution monitoring, and breath diagnostics using a mobile phone.