Synthetic cathinones represent one of the largest groups of new psychoactive substances (NPS), compounds that are being distributed as temporarily legal alternatives to illicit drugs. Apart from this aspect, synthetic cathinones have been intensively studied for their potential medicinal use. Hereby, we discuss some basic considerations for their chiral resolution, which enables the assessment of the biological effect of the individual enantiomers of these drugs. The examples illustrate the utilization of two versatile polysaccharide-based chiral stationary phases (CSPs) in different mobile phases (MPs). Protocols for easy and scalable harvesting of the separated enantiomers are also provided.