The first part of the talk will cover the essential features of modern chiroptical spectroscopies, and the second will illustrate these with several case studies. These will include the rather controversial histories of the determination of the absolute configurations of an important series of sulfur-containing natural products such as the dethiochaetocins and dehydrogliotoxins. The mechanism of dethionation of these species has been claimed to involve both retention and inversion of configuration at the carbon-S centre, and a possible route for either process is shown in the scheme below. Computational chemistry is also used to chart the viability of such a mechanism, although the techniques used to do so require methods that have only recently been introduced as routine procedures. The take-home message is intended to illustrate that the use of computational modeling for both chiroptical spectroscopy and associated mechanistic exploration is increasingly regarded as a sine qua non of the synthetic laboratory.