Numerical models can provide the needed information for understanding hypoxia and ensuring effective management, and this book provides a snapshot of representative modeling analyses of hypoxia and its effects. In this chapter, we used the modeling and analyses across the other 14 chapters to illustrate 8 themes that relate to the general strengths, uncertainties, and future areas of focus in order for modeling of hypoxia and its effects to continue to advance. These themes are role of physics; complexity of the dissolved oxygen (DO) models; oxygen minimum zones (OMZs) and shallow coastal systems; observations; vertical dimension; short-term forecasting; possible futures; and ecological effects of hypoxia. Modeling the dynamics and causes of hypoxia has greatly progressed in recent decades, and modern models routinely simulate seasonal dynamics over 0.1–1 km scales. Despite these advances, prevailing model limitations include uncertain specification of boundary conditions and forcing functions, challenges in representing the sediment-water exchange and multiple nutrient limitation, and the limited availability of observations for multiple contrasting years for model calibration and validation. A major challenge remains to effectively link the water quality processes to upper trophic levels. A variety of approaches are illustrated in this book and show that quantifying this linkage is still in the formative stages. There will be increasing demands for predicting the ecological responses to hypoxia in order to quantify the ecological benefits and costs of management actions and to express the simulated effects of coastal management and climate change in terms of direct relevance to managers and the public.