Based on basic radiobiological principles, we suggest that the radiosurgery technique of delivering a radiation dose in a single fraction, whilst appropriate for benign brain lesions such as arteriovenous malformations (AVM), is not optimal for treating malignant tumors. Radiosurgery was originally developed to treat benign lesions in the brain, such as AVMs, and has been successfully used for this purpose for over four decades. Recently, the technique has been adopted for treating small primary malignant brain tumors or single metastases. We argue, and derive radio-biological data to support the view that, treating malignant tumors with a single fraction will result in a suboptimal therapeutic ratio between tumor control and late effects, even for small tumors; and that improved therapeutic ratios would be expected if the treatment were fractionated into a small number of fractions. On the other hand, no therapeutic gain is to be expected from fractionating treatment of AVMs. A new generation of noninvasive relocatable stereotactic head frames makes feasible the use of fractionated stereotactic external-beam radiotherapy, and may allow significant benefits over single, radiosurgical, treatments for malignant brain tumors. As stereotactic fractionation/protraction regimes become more widespread, a uniform approach for determining equivalent fractionation schemes becomes important for intercomparing clinical results, and such calculations can be reliably carried out using the linear-quadratic formalism.