Older patients disproportionately suffer the burden of infection in the community and in health care facilities. The rational approach to antimicrobial therapy for older patients with infection requires an appreciation and understanding of the complex immunologic, epidemiologic, pharmacologic, and microbiologic factors that influence the manifestations and consequences of infection in this group. Specific recommendations for common infectious syndromes must take into account the unique needs of older patients and should be tailored for each individual case.