<b><i>Background:</i></b> Rapid drug desensitization (RDD) induces a temporary tolerance to chemotherapeutics that induce hypersensitivity reactions (HSRs). <b><i>Purpose:</i></b> Our objective is to report our experience with RDD to platins, taxanes, etoposide, doxorubicin, and irinotecan. <b><i>Methods:</i></b> The study was conducted as a retrospective chart review of patients with symptoms of HSRs to chemotherapeutics. HSRs were classified as grade I, II, or III, based on their severity. Skin prick/intradermal tests were performed with implicated chemotherapeutics. A 12-step RDD protocol was used. <b><i>Results:</i></b> The study consisted of 38 women and 3 men (mean age 53.3 ± 11.6 years). Patients had ovarian (<i>n</i> = 13, 31.8%), breast (<i>n</i> = 10, 24.4%), colon (<i>n</i> = 7, 17%), lung (<i>n</i> = 4, 9.8%), and other cancers (<i>n</i> = 7; endometrial sarcoma, testicular cancer, uterine cancer, ampulla of Vater tumor, choledochal tumor, peritonitis carcinomatosa, and Merkel cell carcinoma, <i>n</i> = 1, respectively). Twenty-two patients experienced HSRs to platins, 15 to taxanes, and 4 to other chemotherapeutics (doxorubicin, irinotecan, and etoposide). A total of 122 RDDs (47 to platins, 52 to taxanes, 23 to other chemotherapeutics) were performed. In 25 (61%) patients no reactions occurred during RDD, but breakthrough reactions developed in 16 patients (39%) with platins (<i>n</i> = 11), taxanes (<i>n</i> = 3), doxorubicin (<i>n</i> = 1), and irinotecan (<i>n</i> = 1). RDD procedures could not be completed in only 2 patients with grade II breakthrough reactions to carboplatin and oxaliplatin. <b><i>Conclusion:</i></b> In our experience, 98.3% of 122 RDDs were completed. We found that RDD was safe and effective in this the largest series of RDD with chemotherapeutics in our country.