The smart grid is a complex system that comprises components from both the power grid and communication networks. To understand the behavior of such a complex system, co-simulation is a viable tool to capture the interaction and the reciprocal effects between a communication network and a physical power grid. In this chapter, we systematically review the existing efforts of cosimulation and propose a framework to explore co-simulation scenarios. Using the demand response and energy price as examples of smart grid applications, and operating the communication network under various conditions (e.g., normal operation, degraded performance, and security threats), we evaluate the performance of smart grid applications by leveraging the co-simulation platform. In addition, we conduct a co-simulation study to investigate the impact of wireless network implementations, including the wireless mesh architecture based on Ad hoc On-Demand Distance Vector (AODV) protocol, and the Worldwide Interoperability for Microwave Access (WiMAX) architecture, on the performance of smart grid applications.