Assessment via MRI is an integral part of the management of primary brain tumors. However, reliance on imaging to determine treatment response is not without its pitfalls. Necrosis is a known late effect of radiation treatment of the brain that can mimic tumor recurrence. It is now appreciated that pseudoprogression, a similar effect, can occur after combined chemoradiotherapy and can occur more quickly and dramatically than after radiation alone. Although several adjunct imaging modalities are under investigation, none is yet widely accepted as being able to distinguish between true progression and pseudoprogression. Conversely, at disease progression, antiangiogenic therapies are frequently used and can have a rapid positive effect on imaging. These changes, increasingly known as "pseudoresponses," can occur immediately after initiating treatment, making accurate assessment of true tumor response difficult. This article reviews the challenges of brain tumor imaging and its use in assessment of treatment response.