Outcome data as well as reported anecdotal experience over the past 20 years indicate that any infection can be safely treated with parenteral antimicrobials outside the hospital setting. However, outpatient parenteral antimicrobial therapy (OPAT) is a reasonable option only when the final decision for patient selection is based on the judgment of a knowledgeable, experienced physician, and when an experienced qualified provider is available. Criteria to be considered include clinical status, patient acceptance, ability to comply with the plan of treatment, home environment, support systems, and reimbursement. Physician direction and participation in appropriate patient selection will become increasingly important as the growth of managed care increases the importance of cost-savings.