The technique for performing brain biopsy has evolved significantly over the last three decades. Intraoperative MRI guidance has enhanced the diagnostic rate for brain biopsy by now allowing neurosurgeons to compensate for brain shift while performing the procedure in near-real time. The development of a trajectory guide enables the neurosurgeon to determine a safe and accurate path for intraoperative MRI-guided brain biopsy and to secure the position of the needle within the target tissue. Magnetic resonance spectroscopy (MRS) has been used to help distinguish recurrent brain tumor from the effect of previous treatments by measuring specific metabolites within the area of concern. Combining the use of a trajectory guide with MRS should enhance the diagnostic yield for MRI-guided brain biopsy.