We report a case of primary cutaneous zygomycosis caused by Rhizopus species in an infant with a hematological malignancy. Multiple surgical debridements, skin grafting, and intravenous antifungal therapy were necessary to ultimately eradicate the infection. Zygomycotic infections are an emerging concern in immunocompromised patients because of their increased incidence as well as their potential to cause substantial morbidity through both emotional distress and impaired functionality. Because resection is a cornerstone of treatment for zygomycosis, the authors anticipate a growing need for plastic surgery involvement for both surgical debridement with limb and tissue-sparing procedures, and for reconstructive options that effectively treat the disease while preserving both function and esthetics. The plastic surgery literature is reviewed regarding surgical and reconstructive options for this population of patients. This case demonstrates the important role plastic surgeons play in the multidisciplinary treatment of zygomycotic and other opportunistic cutaneous infections.