Using data from the 2001–2005 Medical Expenditure Panel Survey, this study shows that nearly 40 percent of nonelderly adults with three or more chronic conditions had out-of-pocket expenses and premiums exceeding 5 percent of income for two consecutive years, compared with 20 percent of people who had a single chronic condition and 14 percent who had no chronic conditions. Prescription drug spending accounts for over half of the out-of-pocket spending by individuals who have multiple chronic conditions and who have had persistently high financial burdens that last two years or more. The prevalence of persons with persistently high financial burdens is likely to increase in the future, because of expected increases in prescription drug costs as well as chronic disease prevalence.