Variation and cost in oncology care represent a large and growing burden for the US health care system, and acute hospital care is one of the single largest drivers. Reduction of unplanned acute care is a major priority for clinical transformation in oncology; proposed changes to Medicare reimbursement for patients with cancer who suffer unplanned admissions while receiving chemotherapy heighten the need. We conducted a review of best practices to reduce unplanned acute care for patients with cancer. We searched PubMed for articles published between 2000 and 2017 and reviewed guidelines published by professional organizations. We identified five strategies to reduce unplanned acute care for patients with cancer: (1) identify patients at high risk for unplanned acute care; (2) enhance access and care coordination; (3) standardize clinical pathways for symptom management; (4) develop new loci for urgent cancer care; and (5) use early palliative care. We assessed each strategy on the basis of specific outcomes: reduction in emergency department visits, reduction in hospitalizations, and reduction in rehospitalizations within 30 days. For each, we define gaps in knowledge and identify areas for future effort. These five strategies can be implemented separately or, with possibly more success, as an integrated program to reduce unplanned acute care for patients with cancer. Because of the large investment required and the limited data on effectiveness, there should be further research and evaluation to identify the optimal strategies to reduce emergency department visits, hospitalizations, and rehospitalizations. Proposed reimbursement changes amplify the need for cancer programs to focus on this issue.