The exact 3D structure of the enigmatic σ1 receptor is unknown, as the crystal structure of this protein has not been solved so far. Many efforts have been devoted to unveiling the structure of the σ1 receptor and specifically its binding site, which include photoaffinity labeling, site directed mutagenesis, and homology modeling. The aim of the present miniperspective is to give a short overview of all results that contribute to the current knowledge of the σ1 receptor and its ligand binding site.