The complex mechanisms of chronic pain require the use of multimodal therapy based on its pathogenesis, however the treatment regimens used include drugs with serotonergic activity, herewith it has been proven that almost all opioid analgesics co-administrated with other serotonergic agents can cause an increase in synaptic serotonin levels, which leads to serotonin syndrome (SS). SS is characterized by mental status changes, neuromuscular hyperactivity, and autonomic instability and it is a potentially life-threatening status. The SS incidence is increasing with the widespread use and new opioid analgesics and antidepressants introduction. The article presents the mechanisms of SS including various opioid analgesics use, gradation of opioid analgesics according to the SS risk degree when used with serotonergic drugs, clinical picture and SS diagnostics, the core measures for therapy and prevention.