In recent years, II-VI compound semiconductor nanoparticles synthesized in a liquid solution have been shown to possess unique optoelectronic properties which are highly attractive for the fabrication of various sensors based on the optical signal readout scheme. The challenge has been to immobilize these nanoparticles into films on solid surfaces, i.e. on a chip, so that they do not suffer any property deterioration as a sensing medium. In the presented work, synthesis of CdS nanoparticles in reverse micelle solution using AOT surfactant as a stabilizer has led to particles with relatively bright photoemission identified as originating from both shallow and deep traps inside the bandgap. Moreover, slightly altering the preparation procedure has produced samples with two distinctive crystal structures. Both types of CdS nanoparticles suspended in commonly utilized solvents such as chloroform and hexane were subject to chemical quenching when various organic compounds were introduced into the solution, demonstrating the sensitivity of trap states to their chemical environment. However, the two structures have shown very different optical properties. While post-synthesis treatment had no effect on one type of particle, the other type was able to undergo a photochemical reaction via prolonged UV irradiation, which resulted in an increased luminescence quantum yield ÖL from 2% to 14%. The same particle type was also responsive to thermal treatment, showing even higher values of ÖL (∼40%). The CdS/AOT particles have been cast into thin films by spin-coating on a Si wafer. Coating parameters have been investigated in order to achieve optimal control over the film thickness, uniformity, overall film durability, etc. These nanostructured films capped with various porous polymeric and sol-gel protective coatings were exposed to a series of organic compounds. Photoluminescence data collected for these samples served for identification of the compounds and their concentrations. This paper offers the discussion of photophysical response in CdS nanoparticle-based thin films with respect to development of novel nanostructured opto-chemical sensors.