Patients with advanced cancer receiving hospice and palliative care are highly susceptible to infections. The decision whether to treat an active or suspected infection in end-of-life care may be difficult. In order to develop guidelines for the use of antimicrobials (antibiotics and antifungals) in palliative care, we discussed antimicrobial options with 255 patients with advanced cancer at the time they entered a community-based hospice and palliative care program. We subsequently documented the use and effectiveness of the antimicrobials employed during the palliative care period. Most patients (79.2%) chose either no antimicrobials or symptomatic use only. Choices were influenced by age, the desire for symptom control, life-prolongation issues, and the condition of the patient. After admission, 117 patients had a total of 129 infections, with the most common sites being urinary tract, respiratory tract, mouth/pharynx, and skin/subcutaneous tissues. The use of antimicrobials controlled symptoms in the majority of the urinary tract infections, but were less effective in controlling symptoms in the other sites of infection. Survival was not affected by the patients' choice of whether to use antimicrobials, the prevalence of infections, or the actual use of antimicrobials. Symptom control may be the major indication for antimicrobial use for patients receiving hospice and palliative care.