Temozolomide (TMZ) is an oral alkylating agent used during concurrent and adjuvant chemotherapy for newly diagnosed glioblastoma multiforme. Temozolomide is generally well tolerated and improves survival; however, severe adverse events have occasionally been reported. Here, we report the case of a patient who developed aplastic anemia with related complications in the setting of concurrent TMZ treatment with radiotherapy. This case illustrates that aplastic anemia is a rare side effect of TMZ that can occur relatively early in the course of concurrent chemotherapy, and underscores the importance of clinician awareness of this potentially devastating side effect.