Midline discharges, lateralized periodic discharges, and seizures have been described with ipsilateral lesions that result in midline shift (MLS). Periodic discharges and seizures arising contralateral to a known lesion have not previously been described as a sign of MLS. We present four patients with focal brain lesions, resulting in MLS and epileptiform discharges arising from the contralateral hemisphere. Patient 1 underwent a right anterior temporal lobectomy. On postoperative day 2, computed tomography demonstrated a right to left MLS of 12 mm, and EEG was remarkable for left temporal nonconvulsive status epilepticus. Patient 2 experienced a subarachnoid hemorrhage, which was more prominent on the left. Computed tomography after craniotomy demonstrated left to right MLS of 6 mm, and EEG was remarkable for right lateralized periodic discharges. Patient 3 had a right subdural hematoma and underwent craniotomy for evacuation. On postoperative day 3, computed tomography demonstrated a right MLS of 7 mm, and EEG was remarkable for left temporal nonconvulsive status epilepticus. Patient 4 had traumatic brain hemorrhages with maximal left frontotemporal involvement. Six days after the trauma, computed tomography was significant for left to right MLS of 9 mm, and EEG showed right lateralized periodic discharges. Epileptiform discharges and seizures occurring contralateral to a known lesion may be an indicator of MLS.