Drug hypersensitivity reactions (HSR) are adverse events resembling allergy which occur at therapeutic doses. Both anticancer chemotherapeutics and monoclonal antibodies have the potential for acute HSR. all infusion reactions involve the immune system; however, some (anaphylactic) are allergic in nature and usually are mediated by immunoglobulin E (IgE), whereas others (anaphylactoid) are not true allergic reactions and are not mediated by IgE. although HSR can be allergic or nonallergic, the clinical manifestations are the same and require prompt, accurate assessment and management to avoid severe adverse events, including fatality. Monoclonal antibodies have a unique side-effect profile that includes the potential for nonallergic HSR caused by cytokine release. Chemotherapeutic agents with the highest potential for acute HSR include the platinum salts, taxanes, procarbazine, asparaginase and the epipodophyllotoxins. From all anticancer agents, rituximab causes the majority of HSR (27%), followed by paclitaxel (10%). The most frequent symptoms in patients experiencing acute HSR include chest pain, dyspnea, wheezing and exanthema for the taxanes, dyspnea and exanthema for platinum salts, chills and rigor for antibodies. Patients with mild-to-moderate acute HSR can be rechallenged following intensified prophylaxis, but rechallenge is usually not recommended following severe HSR.