This chapter discusses the mechanisms whereby Drosophila recognize foreign microbes, the signalling systems that regulate adapted responses against them, and the effector mechanisms used to control them. It first focuses on the so-called systemic antimicrobial response. The second section of the chapter looks at local immune response, particularly gut epithelial immunity. The final section of the chapter discusses current research themes exploring the integration of local and systemic immunity, as well as their integration in host physiology