If discovery of new antibiotics continues to falter while resistance to drugs in clinical use continues to spread, society's medicine chest will soon lack effective treatments for many infections. Heritable antibiotic resistance emerges in bacteria from nonheritable resistance, also called phenotypic tolerance. This widespread phenomenon is closely linked to nonproliferative states in ways that scientists are just beginning to understand. A deeper understanding of the mechanisms of phenotypic tolerance may reveal new drug targets in the infecting organisms. At the same time, researchers must investigate ways to target the host in order to influence host-pathogen relationships. Government must reform the regulatory process for approval of new antibiotics. The private sector, government, and academia must undertake multiple, organized, multidisciplinary, parallel efforts to improve the ways in which antibiotics are discovered, tested, approved, and conserved, or it will be difficult to sustain the modern practice of medicine.