An elderly patient with depression and chronic back pain presents with several months of new onset agitation, insomnia, hyperhidrosis, hypertension, tachycardia, nausea, and vomiting. Her pain quality is unchanged, and basic labs and imaging including cardiac echocardiography are normal. Notably, her medication regimen includes opioids and anti-depressants raising concern for chronic serotonin syndrome. Here, we review the diagnosis of serotonin syndrome and therapeutic considerations for management of the challenging condition.