Aging is associated with a reduced capability of the immune system to adequately respond to pathogens and to prevent tumor formation. As a consequence of immunosenescence, older people have a higher risk to develop infections as well as cancer. In addition, cancer itself may expose old patients to infections, including opportunistic infections, i.e. Pseudomonas aeruginosa, Aspergillus fumigatus and Cytomegalovirus infection. Patients with hematologic malignancies have a higher risk than patients with solid tumors, because of more prolonged disease-related and treatment-related neutropenia and intensive immunosuppressive regimens. Co-existing medical conditions, e.g. chronic renal failure, diabetes mellitus, emphysema, which are quite common in the elderly, may also contribute to rising the infectious risk, as well as the use of long term vascular catheters, which is required in a large number of cancer patients to administrate chemotherapy. Neutropenic infections do not only represent a major cause of morbidity and mortality, but may be responsible for a reduction of the antineoplastic treatment dose and dose intensity, thus compromising the overall treatment effectiveness. The use of antibiotic prophylaxis to reduce neutropenia-related infectious complications in patients with cancer is still object to debate. Quinolones represent the most attractive option, since these drugs have a broad antimicrobial spectrum, systemic bactericidal activity, good tolerability and lack of myelosuppression. However, fluoroquinolone prophylaxis has already been associated with the emergence and spread of resistant bacteria and strictly precludes the subsequent use of fluoroquinolones for initial empirical therapy; in addition, fluoroquinolones should be administered with caution among elderly patients, especially those with more pronounced vascular or degenerative impairment of the central nervous system, cardiac disease or electrolyte disturbances.