Insects maintain a close relationship with microbes in the environment. This interaction has led to the development of the innate immune system, which is responsible for defending the host from a wide range of pathogens. As pathogens evolve to compromise host immunity, immune genes rapidly counter-evolve. In this dissertation, I present studies that answer how the innate immune system of Drosophila responds to a variety of pathogens and how host-pathogen interactions may have shaped the evolution of host cellular immunity. In Chapter 2, I explore how an arms race between Drosophila and its pathogens may have led to selective sweeps and adaptive evolution in the Drosophila cellular immune system. In Chapter 3, I present work on how host responses to infection with various bacteria are crucial in host survival and homeostasis. In Chapter 4, I investigate the role of genes that are expressed in a coordinated manner upon infection and identify key genes for future functional genetic studies. Altogether, these studies provide a clearer mechanistic and population genetic understanding of host-pathogen interactions and Drosophila immunity.