OBJECTIVES: Novel therapies for cancer have been developed that interfere with specific molecules involved in tumor growth. These therapies are generally more expensive than traditional therapies and have drawn scrutiny from healthcare policymakers. Cost-effectiveness analysis (CEA) is an accepted tool to prioritize healthcare interventions. We conducted a review of the CEA literature on these targeted oncologics to determine if their premium prices are justified. METHODS: A systematic review of the cost-effectiveness literature published between January 1997 and May 2007 was conducted for the following agents: alemtuzumab, bevacizumab, bortezomib, cetuximab, erlotinib, gefitinib, gemtuzumab, imatinib, rituximab, sorafenib, sunitinib, tositumomab, and trastuzumab. Exclusion criteria included: publications not available in English, letters to the editor, opinion-based articles, review articles, abstracts only, health technology assessments, and studies of diseases other than cancer. Relevant data from the included articles were extracted to summary tables. RESULTS: Eighteen articles met the inclusion and exclusion criteria. Six articles evaluated trastuzumab for breast cancer, 5 examined imatinib for chronic myelogenous leukemia, and 4 studied rituximab for diffuse large B-cell lymphoma. The remaining 3 articles examined imatinib, bortezomib, and cetuximab therapy for gastrointestinal stromal tumors, multiple myeloma, and metastatic colorectal cancer respectively. Targeted therapeutics exceeded the threshold of 50,000 dollars/euros or 30,000 pounds in only 5 out of 22 scenarios (cetuximab + irinotecan vs. best supportive care, imatinib vs. hydroxycarbamide, imatinib vs. hydroxyurea, imatinib vs. combination therapy (blast crisis), trastuzumab vs. standard chemotherapy). CONCLUSION: Less than half of the targeted oncologics studied have been evaluated by the standard technique of CEA. The majority of the CEAs reviewed adhered to standard CEA methodology and found the targeted therapeutics to be cost-effective using generally accepted thresholds. Considering the significance of the value questions regarding cancer care and the interest of policymakers, more health economic studies using standard CEA techniques are warranted for targeted oncology therapeutics.