For the past 60 years, the goal of conventional cancer therapies has been the eradication of every cancer cell. To this end, patients are subjected to the highest possible doses of radiation and chemotherapy as well as radical surgeries. In the rare case in which eradication was possible, clinicians achieved long-term control of the disease. For the most part, however, upfront eradication is not possible, and despite intensive and very toxic therapies, the patient dies of the disease or of complications of therapy. As our understanding about the role of tumor microenvironment in tumor progression and drug resistance improves, we are realizing that the paradigm of killing all cancer cells may be flawed.