The serous cavities are fluid-filled spaces that surround the lung, heart, and abdomen. One of their main functions is to provide protection and lubrication for their encapsulated organs. In addition to these physiological roles, the serous cavities are rich immune cell reservoirs. Although these cavity-derived immune cells have been studied ex vivo for many years, the past decade has led to substantial advances in serous cavity biology. Importantly, immune mechanisms that occur in these fluid environments and communication networks between these cavities and the tissues that they contain have been elucidated. In this Review, we aim to summarize the current knowledge of cellular and molecular interactions that govern immunology across all serous cavities, comparing animal models and human studies. A deeper understanding of how the serous cavities provide immune protection to the tissues that they encompass is likely to reveal therapeutic avenues for manipulation of these cavities to improve disease outcomes.