The method of unambiguously assigning the handedness of molecules was originated by three chemists: R.S. Cahn, C. Ingold, and V. Prelog and, as such, is also often called the Cahn-Ingold-Prelog rules. In addition to the Cahn-Ingold system, there are two ways of experimentally determining the absolute configuration of an enantiomer:

1. X-ray diffraction analysis. Note that there is no correlation between the sign of rotation and the structure of a particular enantiomer.
2. Chemical correlation with a molecule whose structure has already been determined via X-ray diffraction.

However, for non-laboratory purposes, it is beneficial to focus on the R/S system. The sign of optical rotation, although different for the two enantiomers of a chiral molecule,at the same temperature, cannot be used to establish the absolute configuration of an enantiomer; this is because the sign of optical rotation for a particular enantiomer may change when the temperature changes.