The study of σ receptors began in 1976, when experts believed that they were part of a subfamily of opioid receptors. Later it was discovered that they comprised a single family, which is nowadays divided into two subtypes: σ1 and σ2 receptors. However, no clear conclusions have been drawn about their pharmacological importance, which remained controversial for a long time. The σ1 receptor has a single transmembrane domain and is mostly located in the mitochondria-associated endoplasmic reticulum membrane on many different cells of our body. It is believed that the σ1 receptor may be a new therapeutic target in pathologies such as neuropathic pain, neurodegenerative diseases, stroke, and depression. With an increasing number of agonist and antagonist compounds they are the subject of further clinical studies.