Leukocytes accumulate at sites of inflammation and immunological reaction in response to locally existing chemotactic mediators. The first chemotactic factors structurally defined were N-formyl peptides. Subsequently, numerous ligands were identified to activate formyl peptide receptors (FPRs) that belong to the seven-transmembrane G protein-coupled receptor superfamily. FPRs interact with this menagerie of structurally diverse pro- and anti-inflammatory ligands to possess important regulatory effects in multiple diseases, including inflammation, amyloidosis, Alzheimer's disease, prion disease, acquired immunodeficiency syndrome, obesity, diabetes, and cancer. How these receptors recognize diverse ligands and how they contribute to disease pathogenesis and host defense are basic questions currently under investigation that would open up new avenues for the future management of inflammation-related diseases.