Health care decision makers in many jurisdictions use cost-effectiveness analysis based on health economic decision models for policy decisions regarding coverage and price negotiation for medicines and medical devices. While validation of health economic decision models has always been considered important, many reviews of model-based cost-effectiveness studies report limitations regarding their validation. The current opinion paper discusses four aspects of current health economic decision modeling with relevance for future directions in model validation: increased use of complex models, international cooperation, open-source modeling, and stakeholder involvement. First, new, more complex clinical study designs and treatment strategies may require relatively complex model structures and/or input data analyses. Simultaneously, more widespread technical knowledge along with wider data availability have led to a broader range of model types. This puts extra requirements on model validation and transparency. Second, increased international cooperation of policy makers and, in particular, health technology assessment (HTA) authorities in performing model assessments is discussed in relation to the repeated use of health economic models (multi-use disease models). We argue such coordinated efforts may benefit model validity. Third, open-source modeling is discussed as one possible answer to increased transparency requirements. Finally, involvement of all relevant stakeholders throughout the whole decision process is an ongoing development that necessarily also includes health economic modeling. We argue this implies that model validity should be considered in a broader perspective, with more focus on conceptual modeling, model transparency, accuracy requirements, and choice of relevant model outcomes than previously.