Primary central nervous system lymphoma (PCNSL) is an uncommon variant of extranodal non-Hodgkin lymphoma (NHL) that involves the brain, leptomeninges, eyes or spinal cord without evidence of systemic disease. Despite the high complete remission rate achieved with aggressive first-line therapy, 10–35% of PCNSL are treatment refractory and 35–60% of patients relapse. Standard therapy for recurrent or refractory disease has not yet been established, although retrospective data suggests improvement in survival with salvage therapy. The reported survival after relapse of PCNSL varies between 2 months and 24 months, with most series reporting an average of 4–12 months. The outcomes depend on whether treatment is instituted or not, suggesting a need for treatment guidelines for these patients. We review therapeutic approaches and their outcomes in recurrent or refractory PCNSL.