The serous cavities contain specialised adipose tissues which house small clusters of immune cells known as fat-associated lymphoid clusters (FALCs). The continuous flow of fluid from the serous cavities through FALCs makes them unique niches for the clearance of fluid phase contaminants and initiation of locally protective immune responses during infection and inflammation. Development, and activation of FALCs both at homeostasis and following inflammation are co-ordinated by the close interaction of mesothelial and fibroblastic stromal cell populations with immune cells. In this review we discuss recent developments in FALC stromal cell biology and highlight key interactions that occur between FALC stroma and immune cells.