Molecular sensors are devices that detect, record, and indicate a physical or chemical property, with potential capability for further processing and have a sensitivity and specificity at molecular scales. Key sensing components or the design of many molecular sensors are based on those found in living organisms; natural systems are the original form of molecular sensors. Modern sensor technology may not as sophisticated as those found in nature, but it is improving rapidly with the convergence of information technology, breakthroughs in physical design, and advanced manufacturing. Modern molecular sensors are essential parts of many emerging medical diagnostic devices playing significant roles in global health, reducing healthcare costs in developed countries, and in increasing the response of the world to pandemics or bioterrorism. Prominent areas of molecular sensor research are the detection of biomolecules for disease diagnosis, the detection of volatile components for air pollutant characterization, and the detection of chemical analytes for evaluation of physiological activity. First we describe the actual composition of molecular sensors. A sensor is composed of the three main elements: 1. detector (capture and recognition), 2. transducer (signal transduction), and 3. processor. Molecular sensors employ a variety of capture and recognition mechanisms. For biological molecules, we can use proteins (antibodies, receptors), nucleotides (DNA, RNA, aptamers), synthetic polymers that simulate a binding site, and phages. Through signal transductions, sensors convert the detection event into a measurable signal. Sensors convert a biological, chemical or physical quantity into a detectable signal, mostly an electrical signal. We categorize molecular sensors into three categories based on the transduction principle: electrical transduction, mechanical transduction, and optical transduction. Finally, we look at nature’s natural biosensors by examining the olfactory systems of animals and insects and discuss their applications as molecular sensors.