Only one atom has four different things attached to it. Thalidomide has only one stereocenter, so the stereoisomers must be a set of enantiomers. The physical properties of enantiomers such as solubility or melting point are identical except for the direction in which they rotate plane polarized light. Thus the enantiomers of thalidomide cannot be separated by means that depend on their physical properties alone. In a chiral environment, physical properties might be sufficiently different to allow separation.
Many drugs act by binding to enzymes or receptor sites.
These binding sites have a certain three-dimensional chiral shape that fits a specific arrangement of atoms in space. The binding site may fit one enantiomer of thalidomide, producing a certain biological effect. The other enantiomer has a mirror image shape, so the arrangement of atoms in space is different. This different arrangement of atoms may not fit the same binding site, but instead may fit into a separate binding site, resulting in a different effect. This is analogous to a lock and key arrangement.