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Anti-CD20 therapies deplete B cells and blunt humoral responses, reducing vaccine efficacy for months. When possible, complete inactivated vaccines at least 2–4 weeks before starting therapy to allow an immune response. During treatment, inactivated vaccines (e.g., influenza) may be given but responses are suboptimal; revaccination or booster strategies may be needed after immune reconstitution. Live vaccines are contraindicated during and for a period after anti-CD20 therapy due to risk of vaccine-related infection. Most guidelines recommend deferring routine vaccinations until ≥6 months—often up to 12 months—after the last rituximab dose to improve serologic responses, individualized by counts and clinical status. Declaring vaccines “unnecessary” (Option D) ignores preventable morbidity. The APRN reviews immunization history, prioritizes influenza annually and pneumococcal/COVID-19 per current schedules, coordinates timing around treatment cycles, and educates on household “cocooning.” Document plans in the EHR and revisit post-therapy to update titers/boosters, optimizing protection while balancing oncologic timelines.