A number of cost-effectiveness models have been developed with the aim of providing guidance for decision making on biologic therapies for the management of inflammatory joint disease. The findings of these analyses can differ markedly, and these differences can undermine the credibility of such models if unexplained. To allow differences between models to be identified more easily, we define six components common to all models-initial response, longer term disease progression, mortality, quality-adjusted life year estimation, resource use and the selection and interpretation of data. We give examples of divergent approaches taken by model structures to the same issue, and explore the impact of divergence on model results, with particular focus on two models that have reported substantially different estimates for the cost-effectiveness of third-line etanercept vs conventional DMARD. The sensitivity of results to a particular assumption made in a model will depend on the decision problem and assumptions made elsewhere in the model, highlighting the importance of guidance throughout model development. To some extent, guidance from bodies such as the National Institute of Health and Clinical Excellence can be used to determine which approach should be preferred where models differ. However, there is a pressing need for clinical input and guidance before consensus can be reached on the most credible model(s) to use for decision support.