Reuse of reclaimed wastewater (RWW) for agricultural irrigation is becoming an essential practice in many arid and semi-arid regions of the world to save fresh water. Additionally, RWW contains essential plant nutrients (e.g., P, N, K), thus limiting the use of chemical fertilizers by farmers, who in the next years would need to substantially intensified their agriculture capacity to meet the increasing food demand. However, as consequences of human activities, other chemicals such as pharmaceuticals and biocides, currently referred to as “contaminants of emerging concern (CECs),” end up in RWW and subsequently in edible part of the crops, posing a risk for the environment and human health. This chapter aims at illustrating how modeling tools can help water managers in the identification of both effective monitoring campaigns and optimal RWW management strategies to minimize risk associated to conventional pollutants and especially to CECs. In fact, models can support the selection among the many hundred chemicals present in wastewater those of highest concern, but also address proper barrier identification once that a desired tolerable risk is set for specific CECs. The chapter illustrates how a RWW reuse system can be conceptualized into mathematical models, with a level of detail allowing to fully understand the processes taking place in each element of the system (wastewater treatment plant, distribution network, soil/plant) and to correctly interpret the simulation results. Two practical examples are also reported, showing the advantages of using modeling tools in risk management in complex RWW reuse systems.