New therapeutic solutions have emerged in the last few decades with the growth and expansion of the field of cancer research. Amongst these new agents, immunotherapy has been prominent, particularly regarding the treatment of hematologic malignancies. One of the most worrisome complications of immunotherapy is cytokine release syndrome (CRS), which represents a supraphysiologic response resulting in excessive release of cytokines and a wide range of systemic manifestations. In this case report, we present a case of cytokine release syndrome following blinatumomab therapy despite premedication with dexamethasone.