The standard of care for newly diagnosed malignant glioblastoma entails postoperative radiotherapy and adjuvant chemotherapy with temozolomide. There has been an increase in the incidence of enhancing and progressive lesions seen on magnetic resonance imaging (MRI) following treatment. Conventional MRI with gadolinium contrast is unable to distinguish between the effects of treatment and actual tumor recurrence. New modalities have provided additional information for distinguishing treatment effects from tumor progression but are not 100% sensitive or specific in diagnosing progression. Novel radiographic or nonradiographic biomarkers with sensitivity and specificity verified in large randomized clinical trials are needed to detect progression.