The number of drugs used for the treatment of different types of cancers is constantly increasing and actually exceeds 100 distinct chemical formulations. The use of most cytotoxic agents is associated with potential hypersensitivity reactions, and the constant increase of their administration has caused an increase in incidence of these adverse effects, thus becoming a relevant problem for clinicians. Hypersensitivity reactions are common with platinum compounds, L-asparaginase, taxanes, procarbazine, and epipodophyllotoxins, whereas they are unusual, but always possible, with the other chemotherapeutic drugs. Reactions associated with individual drugs are discussed in detail. The mechanism underlying these hypersensitivity reactions involves IgE-mediated hypersensitivity reactions, nonallergic hypersensitivity reactions, and a few pathogenetically unclear reactions. More studies are needed to better understand, diagnose, treat, and prevent these reactions. To achieve this goal, a multidisciplinary approach to treat patients with cancer who have potential allergies is needed.