Model-based economic evaluations should capture the impact on all costs and outcomes relevant to the chosen study perspective and time horizon. This editorial defines what is meant by direct treatment disutility (DTD) and describes why it could be an important harm that those designing model-based evaluations should consider. Some existing estimates of DTD identified from the current literature are summarised in terms of the methods used to elicit the values and the size of the estimated DTD. Model-based studies that include DTDs are also summarised. It was found that the values used within model-based economic evaluations (ranging from 0.00384 to 0.02) were typically smaller than the directly elicited values from the existing literature (0–0.033). Yet even with conservative estimates of DTDs, cost-effectiveness results were sensitive to their inclusion. The editorial concludes by discussing future methodological and empirical research needed to estimate more robust DTD values.