Intracranial metastatic disease (IMD) is a common and severe complication of primary cancers. Current treatment options for IMD include surgical resection and radiation therapy, although there has been recent interest in targeted therapy in the management of IMD. As of yet, insufficient data exist to support the recommendation of targeted therapies in the treatment of IMD. Paradoxically, targeted therapy has been hypothesized to play a role in the development of IMD in patients with primary cancers. This is based on the observations that patients who receive targeted therapy for primary cancer experience prolonged survival, and that prolonged survival has been associated with increased incidence of IMD. Few data exist to clarify if treatment of primary cancers with targeted therapies influences IMD incidence. Here, we discuss the role of targeted therapy in IMD management, review the current literature on IMD incidence and targeted therapy use in primary cancer, and propose the need for future studies to inform physicians in choosing treatment options and counseling patients.