Patients with brain tumors are routinely monitored for tumor progression and response to therapy using magnetic resonance imaging (MRI). Although serial changes in gadolinium enhancing lesions provide valuable information for making treatment decisions, they do not address the fate of non-enhancing lesions and are unable to distinguish treatment induced necrosis from residual or recurrent tumor. The introduction of a non-invasive methodology, which could identify an active tumor more reliably, would have a major impact upon patient care and evaluation of new therapies. There is now compelling evidence that magnetic resonance spectroscopic imaging (MRSI) can provide such information as an add-on to a conventional MRI examination. We discuss data acquisition and analysis procedures which are required to perform such serial MRI-MRSI examinations and compare their results with data from histology, contrast enhanced MRI, MR cerebral blood volume imaging and FDG-PET. Applications to the serial assessment of response to therapy are illustrated by considering populations of patients being treated with brachytherapy and gamma knife radiosurgery.