Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with distinct pathologic and clinical characteristics. Unlike the malignant cells in classical Hodgkin lymphoma, the disease-defining lymphocyte-predominant cells in NLPHL are consistently positive for CD20, but do not express CD30. The clinical course of NLPHL is indolent in the majority of cases. Most patients present with early-stage disease at the initial diagnosis. First-line treatment of stage IA NLPHL usually consists of limited-field radiotherapy alone. Patients with early-stage NLPHL other than stage IA and intermediate-stage disease mostly receive combined-modality treatment, whereas individuals with advanced NLPHL are treated with chemotherapy alone. In relapsed NLPHL, conventional chemotherapy, anti-CD20 antibodies, and radiotherapy represent active treatment modalities. Only patients with poor-risk characteristics such as early disease recurrence are candidates for aggressive salvage treatment with high-dose chemotherapy and autologous stem cell transplantation. The overall and relative survival of patients with NLPHL is excellent as indicated by a low excess mortality compared with the general population. This article discusses treatment options for patients with NLPHL and factors that influence the choice of therapy on the basis of the available data and 2 clinical cases.