The history of natural as well as medical sciences is full of fascinating stories: some discoveries were caused by mistake and some were actually not firstly perceived as new findings. Discovery and detailed research of sigma receptors belong to such stories undoubtedly. It is a terminated tale - the endogenous ligand was discovered, even if most recently. On the contrary, still some tesseras are missing in this complicated mosaic which such new receptor system represents: it still remains unclear what is their primary role in biological systems and in their regulation. This review is focused on cardiovascular effects of typical representatives of sigma receptor ligands and – at the same time clinically widely used antipsychotics – haloperidol and perphenazine. Use (or even abuse) of various antipsychotics represents worldwide trend within last few decades and thus studies focused on their side effects become a high priority. Moreover, cardiovascular system disorders belong to the most common causes of morbidity and mortality in the developed countries. A significant group of these disorders is represented by side effects of non–cardiovascular drugs.