Cytokine release syndrome (CRS) is a life threatening toxicity associated numerous immunotherapeutic techniques involving monoclonal antibodies, bispecific antibodies and adoptive T cell therapies. It is also referred as infusion reaction that results in release of large amount cytokines (Like IL-6, IFN-r, INF) from the target cells. Cytokines when released in excessive amounts into the circulation produces systemic symptoms like nausea, shills, fever, rashes, headache, hypotension, dyspenea etc. Most of the patients present mild to moderate symptoms which can be managed easily but some patients show life threatening symptoms. Studies have shown that immunosuppressive agents like corticosteroids and tocilizumab can reverse the toxicity of CRS, however such immunosuppression may limit the immunotherapeutic efficacy. Therefore specific precautions must be considered in such patients to present exacerbation of the complication. Thus this review is based on the overview of CRS which include etiology, mechanism and management of CRS, so that immunotherapeutic benefits can be maximized with minimum risk of complication.