BACKGROUND: Non-communicable diseases (NCDs), while traditionally considered a "rich world"-problem, have been spreading fast in low and middle income countries and by now account for a large share of mortality and ill-health in these countries, too. In addition to the disease burden, NCDs may also impose a substantial economic cost. One way in which NCDs might impact people's economic well-being may be via the out-of-pocket expenditures required to cover treatment and other costs associated with suffering from an NCD. METHODS: In this commentary, we identify and discuss the methodological challenges related to cross-country comparison of-out-of-pocket and catastrophic out-of-pocket health care expenditures, attributable to NCDs, focussing on low and middle income countries. RESULTS: There is significant evidence of substantial cost burden placed by NCDs on patients living in low and middle income countries, with most of it being heavily concentrated among low socioeconomic status groups. However, a large variation in definition of COOPE between studies prevents cross-country comparison. In addition, as most studies tend to be observational, causal inferences are often not possible. This is further complicated by the cross-sectional nature of studies, small sample sizes, and/or limited duration of follow-up of patients. Most evidence for certain conditions (e.g., cancer) tends to be collected in high-income countries only. CONCLUSIONS: The definitions for COOPEs should be standardized as much as possible, to enable comparison of COOPE prevalence between countries. Prospective study design using larger samples representative of broader sections of local population, collecting better data on both direct and indirect treatment costs is also needed.