A versatile sensing method based on monodisperse liquid crystal (LC) emulsion droplets detects and distinguishes between different types of bacteria (Gram +ve and −ve) and viruses (enveloped and non-enveloped). LCs of 4-cyano-4'-pentylbiphenyl transition from a bipolar to radial configuration when in contact with Gram −ve bacteria (E. coli) and lipid-enveloped viruses (A/NWS/Tokyo/67). This transition is consistent with the transfer of lipid from the organisms to the interfaces of the micrometer-sized LC droplets. In contrast, a transition to the radial configuration is not observed in the presence of Gram +ve bacteria (Bacillus subtilis and Micrococcus luteus) and non-enveloped viruses (M13 helper phage). The LC droplets can detect small numbers of E. coli bacteria (1–5) and low concentrations (104 pfu mL−1) of A/NWS/Tokyo/67 virus. Monodisperse LC emulsions incubated with phosholipid liposomes (similar to the E. coli cell wall lipid) reveal that the orientational change is triggered at an area per lipid molecule of ∼46 Å2 on an LC droplet (∼1.6 × 108 lipid molecules per droplet). This approach represents a novel means to sense and differentiate between types of bacteria and viruses based on their cell-wall/envelope structure, paving the way for the development of a new class of LC microdroplet-based biological sensors.