Older patients with cancer who may be more susceptible than younger patients to the myelosuppressive effects of chemotherapy undergo dose delays and reductions that can compromise treatment outcomes. Incidence of neutropenic complications and suboptimal chemotherapy delivery can be reduced with prophylactic colony-stimulating factors; however, their use in older patients with cancer has not been well studied. A randomized, multicenter, community-based trial was designed to compare prophylactic pegfilgrastim use (all cycles of chemotherapy) versus its more common reactive use (at clinicians' discretion) in patients aged 65 years or older with various cancers. Pegfilgrastim use in all cycles reduced the incidence of febrile neutropenia by about 60% and hospitalizations caused by neutropenia and febrile neutropenia by about 50% versus reactive pegfilgrastim use in later cycles. The study showed that older patients with cancer can be treated safely with optimal doses of chemotherapy with appropriate supportive care. Nurses, key collaborators in providing supportive care, can take an active role in identifying older patients who may benefit from pegfilgrastim in all cycles of chemotherapy.