Biosensors are powerful analytical tools for biology and biomedicine, with applications ranging from drug discovery to medical diagnostics, food safety, and agricultural and environmental monitoring. Typically, biological recognition receptors, such as enzymes, antibodies, and nucleic acids, are immobilized on a surface, and used to interact with one or more specific analytes to produce a physical or chemical change, which can be captured and converted to an optical or electrical signal by a transducer. However, many existing biosensing methods rely on chemical, electrochemical and optical methods of identification and detection of specific targets, and are often: complex, expensive, time consuming, suffer from a lack of portability, or may require centralised testing by qualified personnel. Given the general dependence of most optical and electrochemical techniques on labelling molecules, this review will instead focus on mechanical and electrical detection techniques that can provide information on a broad range of species without the requirement of labelling. These techniques are often able to provide data in real time, with good temporal sensitivity. This review will cover the advances in the development of mechanical and electrical biosensors, highlighting the challenges and opportunities therein.