First-line treatment selection in follicular lymphoma is closely tied to tumor stage, disease burden, and patient-specific factors. Early-stage presentations may be managed with localized modalities, while advanced disease often calls for systemic chemoimmunotherapy or targeted approaches. Clinicians may shift between first-line options when patients experience intolerance, incomplete response, or evolving clinical features that warrant a different therapeutic intensity. Because initial therapies can lose effectiveness over time, timely transition to second-line regimens becomes essential. This shift is typically prompted by true relapse rather than suboptimal but stable response. Treatment-refractory patients are generally those who fail to respond adequately or progress shortly after therapy, signaling the need for alternative mechanisms of action.