Despite major therapeutic advances in the management of patients with systemic malignancies, management of brain metastases remains a significant challenge. These patients often require multidisciplinary care that includes surgical resection, radiation therapy, chemotherapy, and targeted therapies. Complex decisions about the sequencing of therapies to control extracranial and intracranial disease require input from neurosurgeons, radiation oncologists, and medical/neuro-oncologists. With advances in understanding of the biology of brain metastases, molecularly defined disease subsets and the advent of targeted therapy as well as immunotherapeutic agents offer promise. Future care of these patients will entail tailoring treatment based on host (performance status and age) and tumor (molecular cytogenetic characteristics, number of metastases, and extracranial disease status) factors. Considerable work involving preclinical models and better clinical trial designs that focus not only on effective control of tumor but also on quality of life and neurocognition needs to be done to improve the outcome of these patients.