It is well known that organic Rankine cycle (ORC) power systems often operate in conditions differing from the nominal design point due to variations of the heat source and heat sink conditions. Similar to a vapor compression cycle, the system operation (e.g., subcooling level, pump cavitation) and performance (e.g., heat exchanger effectiveness) of an ORC are affected by the working fluid charge. This chapter presents a discussion of the effects of the charge inventory in ORC systems. In particular, both numerical and experimental aspects are presented. The importance of properly predicting the total amount of working fluid charge for optimizing design and off-design conditions is highlighted. Furthermore, an overview on state-of-the-art modeling approaches is also presented.