Chromatography with supercritical fluids (SFC) is a powerful tool for carrying out separations of substances with very similar structure and volatility, such as isomers of various kinds. In this contribution, we discuss the separation process aiming at the recovery of products on a much larger scale than analytical. Nevertheless, for developing such a process, the separation is carried out first on analytical scale to determine optimum operating conditions and select stationary phase, mobile phase, and co-solvent (modifier), if necessary. Determination of isotherms is helpful for simulating the separation process. Verification of the separation process includes the recycling of the mobile phase. The chromatographic process can be a batch process in the elution mode, or a continuous process, approximated as simulated moving bed (SMB). The batch SFC process, although using a higher quantity of mobile phase is less cost intensive than the SFC-SMB process.