Objective The objectives were to assess the feasibility of using a novel, comprehensive chaplain‐led spiritual life review interview to develop a personal Spiritual Legacy Document (SLD) for persons with brain tumors and other neurodegenerative diseases and to describe spiritual well‐being (SWB), spiritual coping, and quality of life (QOL) of patients and their support persons (SP) before and after receipt of the SLD. Methods Patient‐SP pairs were enrolled over a 2‐year period. Assessments included the Functional Assessment of Chronic Illness Therapy‐Spiritual Expanded Version, Brief Religious Coping Scale, Brief COPE Inventory, and QOL Linear Analog Scale. Baseline assessments were completed prior to an audio‐recorded spiritual life review interview with a chaplain. Results Thirty‐two patient/SP pairs were enrolled; 27 completed baseline assessments and the interview. Twenty‐four reviewed their SLD and were eligible for follow‐up. A total of 15 patients and 12 SPs completed the 1‐month follow‐up; 10 patients and seven SPs completed the 3‐month follow‐up. Patients endorsed high levels of SWB and spiritual coping at baseline. Both patients and SPs evidenced improvement on several aspects of SWB, spiritual coping, and QOL at 1 month, but patients' decreased financial well‐being was also observed. Patients and SPs demonstrated favorable changes in peacefulness and positive religious coping at both time points. Conclusions A chaplain‐led spiritual life review is a feasible intervention for patients with neurodegenerative disease and results in beneficial effects on patients and SPs. Copyright © 2015 John Wiley & Sons, Ltd.