In evaluating the cost/effectiveness of therapeutic interventions (e.g. those based on innovative drugs or on Class-III medical devices), two main pharmacoeconomic parameters have been used over the past decades: the incremental cost-effectiveness ratio (ICER [1–3])1 and the net monetary benefit (NMB [4–6])1. The ICER and the NMB share some common features because they both require a pre-defined willingness-to-pay threshold (WTPt) and the acceptance of quality-adjusted life years (QALYs). Despite this, the differences between these two parameters prevail over the common features, and involve both theoretical and practical issues that can be summarised as follows: (i) the ICER is more suitable for speculative pharmacoeconomic research, whereas the NMB has a more “practical” nature and deals with the application of pharmacoeconomics in real life; (ii) from a mathematical viewpoint, the ICER is more complex than the NMB because the relationship between ICER and costs is nonlinear while the relationship between NMB and costs is linear; (iii) the “typical” health professionals, who are likely to be involved in real-life pharmacoeconomic decisions, are more familiar with ICER than with NMB, whereas the opposite would be preferable; (iiii) as a matter of fact, the ICER is used much more frequently than the NMB, but this simply reflects the greater use of pharmacoeconomics for speculative purposes than for practical applications.