Purpose. Cancer patients carry rising burdens of health carerelated out-of-pocket expenses, and a growing number of patients are considered "underinsured." Our objective was to describe experiences of insured cancer patients requesting copayment assistance and to describe the impact of health care expenses on well-being and treatment. Methods. We conducted baseline and follow-up surveys regarding the impact of health care costs on well-being and treatment among cancer patients who contacted a national copayment assistance foundation along with a comparison sample of patients treated at an academic medical center. Results. Among 254 participants, 75% applied for drug copayment assistance. Forty-two percent of participants reported a significant or catastrophic subjective financial burden; 68% cut back on leisure activities, 46% reduced spending on food and clothing, and 46% used savings to defray out-of-pocket expenses. To save money, 20% took less than the prescribed amount of medication, 19% partially filled prescriptions, and 24% avoided filling prescriptions altogether. Copayment assistance applicants were more likely than nonapplicants to employ at least one of these strategies to defray costs (98% vs. 78%). In an adjusted analysis, younger age, larger household size, applying for copayment assistance, and communicating with physicians about costs were associated with greater subjective financial burden. Conclusion. Insured patients undergoing cancer treatment and seeking copayment assistance experience considerable subjective financial burden, and they may alter their care to defray out-of-pocket expenses. Health insurance does not eliminate financial distress or health disparities among cancer patients. Future research should investigate coverage thresholds that minimize adverse financial outcomes and identify cancer patients at greatest risk for financial toxicity. TheOncologist 2013;18:381-390Implications for Practice: The number of insured patients is increasing, but insured patients are paying more out of pocket for cancer care due to increased cost sharing. As a result, the number of underinsured cancer patients is increasing. Patients are faced with greater out-of-pocket health care costs, but treatment decision making is often made without consideration of these expenses. In our study, insured patients undergoing cancer treatment and seeking copayment assistance experienced considerable subjective financial burden, and they altered care to defray out-of-pocket expenses. Health insurance does not eliminate financial distress or health disparities among cancer patients. Financial distress or "financial toxicity" as a result of disease or treatment decisions might be considered analogous to physical toxicity and might be considered a relevant variable in guiding cancer management. Understanding how and among whom to best measure financial distress is critical to the design of future interventional studies.