Liquid crystals (LCs) are often known as electronic displays and have become ubiquitous in our daily life, apart from that, in the past 10 years, LCs have been investigated as exquisitely sensitive reporters for developing new molecular sensing and detection tools. The unique and primary advantage of this class of intriguing materials is the perturbation of the local ordering LCs at molecular scale by bio/chemical species can be communicated within LC molecules and extended over microns, allowing the observation of the optical signals by microscope or even the naked eye. Therefore, it provides a new platform for developing bio/chemical detection and potentially label-free sensing systems. In March 1888, a young botanist called Friedrich Reinitzer [1] first found that esters of cholesterol appeared to have two melting points between which the liquid showed iridescent colors and birefringence. Actually he discovered a new phase of matter: a liquid crystalline phase, distinguished from solids, liquids and gases that are already familiar to us [2]. Substances in this fourth state are called liquid crystals (LCs), flowing like a conventional liquid and exhibiting orientational order like a crystalline solid. In general, the molecules forming LCs are anisotropic, either rod-like or disc-like. There are two basic classes of LCs: thermotropic and lyotropic. In the thermotropic system, the liquid crystalline phase only exists within a particular temperature range, between a melting point, T m , and an upper transition temperature, T c (Figure 1). In the lyotropic system, LCs possess polar and non-polar parts within the same molecule. In a certain concentration range, molecules organize themselves into ordered structures showing LC properties. This review will not discuss lyotropes further and focus on thermotropic LCs, especially 4-cyano-4′-pentylbiphenyl (5CB), which exhibits liquid crystallinity in the nematic phase at room temperature, a simple and handy choice for constructing optical detectors performed at ambient condition. The key principle of employing LCs for molecular detection is illustrated in Figure 2. The local interruption of LC ordering at the molecular scale can be amplified to micron