Introduction: Follicular lymphoma is the most common indolent lymphoma and remains incurable for the majority of patients despite recent major advances. The disease is typically initially chemosensitive, however relapse is inevitable. In contrast to the frontline setting, studies addressing the optimal timing of initiating second line therapy have not been performed and subsequently practice varies considerably. Areas covered: In the review, we consider the available literature regarding timing of therapy in patients with follicular lymphoma and consider key insights from FL biology to provide guidance on when to treat patients with relapsed disease. Expert commentary: We recommend re-biopsy at time of relapse, immediate treatment of patients with histologic transformation. Treatment for those with recurrent follicular lymphoma may be safely delayed in the absence of bulk, compressive or constitutional symptoms, cytopenias related to lymphoma or steady progression. Patients with localized relapse may be considered for radiotherapy if the involved field would result in minimal toxicity.