Des Smith has made important contributions to the physics of optical coatings, magneto-optics of semiconductors, satellite meteorology, infrared spectroscopy and fluorescence technology and applications. His work has led to highlights such as the tuneable spin-flip Raman laser, which gives the highest resolution molecular gas spectra, and the invention of the carbon dioxide Selective Chopper for the Nimbus 4 satellite temperature sounder — launched in 1970, with derivatives on NASA planetary probes. These included special band pass interference filters.

In 1970, he left the University of Reading for the Chair of Physics at Heriot-Watt University, where he created a research-driven physics department from a green field. He transferred his Reading research group to Edinburgh and introduced optoelectronics to the Scottish universities, becoming Chairman of the Scottish Optoelectronics Association (SOA).

The Riccarton campus included a research park where he founded the first spin-off SME, Edinburgh Instruments, which manufactures and exports lasers, fluorescence spectrometers and infrared gas sensors. Des now chairs Edinburgh Biosciences, which develops cataract diagnosis and treatment by LED and surgical instrument screening.