Sigma-1 ligands have demonstrated potentials as neuroprotective, antiepileptic, and antiamnesic agents in the modulation of opioid analgesia, and in the modification of cocaine-induced locomotor activity. On the other hand, sigma-2 agonists induce apoptosis in drug-resistant cancer cells and may be useful in the treatment of drugresistant cancers. Sigma-2 antagonists might prevent the irreversible motor side effects of typical neuroleptics.