Chemotherapy is typically not given concurrently with whole brain radiation therapy (WBRT) for treatment of metastatic disease due to increased risk of myelosuppression and neurotoxicity. The goal of this study was to evaluate the prevalence, outcomes, and toxicities of concurrent delivery of systemic therapy with stereotactic radiosurgery (SRS) for treatment of brain metastases. We conducted a retrospective review of 196 patients treated with at least one course of SRS without WBRT for brain metastases between 2009 and 2014. Outcome metrics included the administration of concurrent systemic therapy, grade of myelosuppression, development of neurological symptoms, and overall survival. 196 patients with a median age of 61 years (range, 27-85 years) underwent a total of 290 SRS treatments, with a median of 2 lesions targeted per treatment. Histology included non-small cell lung cancer (40%), melanoma (18%), breast cancer (14%), renal cell cancer (9%), and other (18%). 39% of SRS treatments were delivered concurrently with systemic therapy (i.e. systemic therapy started prior to or during SRS and continued through SRS), of which 51% were with conventional myelosuppressive chemotherapy agents, and 49% were with less-myelosuppressive targeted and hormonal agents. The most common systemic agents included platinum chemotherapies (given with 35% of treatments), ipilimumab (17%), taxanes (16%), pemetrexed (13%), and trastuzumab (13%). Systemic therapy was given during the same week as SRS treatment in 79% of cases. Myelosuppression was minimal in patients treated with both systemic therapy and SRS, with median grade 0 leukopenia, neutropenia, and thrombocytopenia, and grade 1 lymphopenia and anemia over the 1 month following treatment. Grade 3-4 toxicity was minimal (9% of lymphopenia and 3-5% of leukopenia, neutropenia, anemia, and thrombocytopenia) and primarily seen in patients treated with conventional myelosuppressive agents. 52% of patients who received systemic therapy and SRS had neurological symptoms during the 1 month following treatment, and these included fatigue (62%), headache (21%), weakness (15%), and gait instability (15%). Patients treated with myelosuppressive versus non-myelosuppressive agents, as well as systemic therapy given within the same week or not, were equally likely to develop neurological symptoms. Dexamethasone was used in 26% of cases in the month following treatment. Median overall survival for the cohort was 16.9 months following SRS. Systemic therapy can be safely given concurrently with SRS for brain metastases, and this is an attractive option for patients who have both intracranial and extracranial metastatic disease. Our results suggest minimal myelosuppression and neurotoxicity across different systemic agents, even when delivered within the same week as SRS.