Among the family of lipid-derived mediators, the group of lysophospholipids including lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) have growth-related and -unrelated effects on diverse cell types including lymphocytes, macrophages, smooth muscle cells, endothelial cells, and neuronal cells. This review summarizes the known effects of lysophospholipids and their G protein-coupled receptors (GPCRs) in inflammation and immunity. Lysophospholipids have the capacity to evoke and modulate immune responses by attracting and activating T-cells, B-cells and macrophages directly and influencing their interactions with other cell types. Immune cells express multiple subsets of lysophospholipid receptors, which are critical for specific cellular responses such as proliferation and migration that are fundamental to immunity. Investigation of the expression pattern of EDG-receptors on human T-cells revealed a dynamic transcriptional regulation influenced by both developmental stages and activation states. Other lipid mediators like psychosine and other GPCRs for lipid mediators like G2A also may be involved in the development of normal immune and inflammatory reactions and diseases. These observations suggest that agonists and antagonists for lysophospholipid receptors may influence immune responses.