In the 21st century, single enantiomeric chiral active pharmaceutical ingredients (APIs) prevail among new drugs. Their preparation is made easier by using direct methods for the separation of racemates. The history of this issue is summarized and information about new and updated methods of conglomerate identification and practical implementation options for direct resolutions is provided. Examples are given for the application of direct methods for obtaining enantiopure APIs by the resolution of their racemic synthetic precursors, using a slight modification of the target product and finally by direct resolution of the racemic chiral drugs as such.