Despite recent advances in both technology and molecular targeting, little progress has been made in the management of most malignancies of the brain, especially brain metastases. In an effort to increase the therapeutic ratio of external beam radiation treatments, radiosensitizers and enhancers have been investigated. Motexafin gadolinium is a new drug with radioenhancing properties and a unique mechanism of action that may increase the therapeutic index of whole brain radiotherapy for patients with brain metastases. The rationale for the use of this drug as well as its current and future role as a radiation enhancer in the management of brain tumors is reviewed.