This review provides an overview of chemotherapy-induced hypersensitivity reactions and the evolving strategies for desensitization. Chemotherapy remains the cornerstone in cancer treatment but chemotherapy-related hypersensitivity reactions, including anaphylaxis, pose significant clinical challenges that compromise patient safety in receiving these life-sustaining treatment. The incidence of chemotherapy-associated hypersensitivity reactions is approximately 5 %, with platinum-based agents being the most likely to induce severe reactions. Desensitization protocols have emerged as crucial strategies to mitigate hypersensitivity reactions, enabling patients to safely continue essential chemotherapy. Two primary categories of desensitization exist: rapid drug desensitization and slow drug desensitization. Rapid drug desensitization, which achieves therapeutic doses within 4−12 h, is primarily used for immediate hypersensitivity reactions. Various protocols, including three-bag, twelve-step; four-bag, four-step; and one-bag protocols, have been developed, each with varying efficacy and safety profiles. One bag protocols, which are currently recommended for low risk patients, need to be further evaluated for safety and efficacy before wide implementation. Risk stratification through medical history, skin testing, and drug challenges plays a vital role in determining eligibility for desensitization. Skin testing has proven useful in assessing hypersensitivity, especially to platinum salts. Overall, desensitization has shown to be a generally safe and effective treatment, achieving high completion rates even in cases of breakthrough hypersensitivity.