A significant amount of literature is available on treatment monitoring and response assessment in lymphoma using FDG-PET, yet confusion exists concerning the potential and limitations of FDG-PET for determining the presence of residual disease during chemotherapy (interim FDG-PET). This article reviews the role of interim FDG-PET in 3 important scenarios: untreated diffuse large B-cell lymphoma, untreated Hodgkin lymphoma, and relapsed or refractory aggressive lymphoma in transplant-eligible patients, and provides recommendations on the use of this imaging modality in these settings.