Brain damage can occasionally result in paradoxical functional benefit, which could help identify therapeutic targets for neuromodulation. However, these beneficial lesions are rare and lesions in multiple different brain locations can improve the same symptom. Using a technique called lesion network mapping, we show that heterogeneous lesion locations resulting in tremor relief are all connected to common nodes in the cerebellum and thalamus, the latter of which is a proven deep brain stimulation target for tremor. These results suggest that lesion network mapping can identify the common substrate underlying therapeutic lesions and effective therapeutic targets. Ann Neurol 2018;83:153–157