Purpose of the Review <p>Nicolau’s syndrome (NS) is a rare but serious drug reaction that occurs after administration of many drugs through various routes, with a broad spectrum of manifestations ranging from severe pain up to skin necrosis. In this review, we reported a case of advanced-grade NS following intravenous injection of ibuprofen. Moreover, we reviewed the existing knowledge and current practice to present in-depth any possible pathogeneses involved in this condition and highlight the specific pharmacological properties of the offending drugs that may play a role in the development of this syndrome. Eventually, we provided recommendations to prevent and treat the incidence of NS, with a focus on the therapeutic role of stellate ganglion block as a novel intervention in such cases.</p> Recent Findings <p>We reported a case of Nicolau’s syndrome after iatrogenic intravenous injection of ibuprofen, which caused severe upper limb ischemia. Notably, the condition was successfully managed with stellate ganglion block, representing a promising effective approach in the management of this serious complication.</p> Summary <p>Early Stellate ganglion block may help in treating this condition effectively with its vasodilatory effect. To our knowledge, it is the first time stellate ganglion block has been implemented in managing this syndrome,&#xa0;fostering new hope in curing these cases.</p>