The formyl peptide receptors (FPRs) are G protein coupled receptors that recognize a broad range of structurally distinct pathogen and danger-associated molecular patterns and mediate host defense to infection and tissue injury. It became evident that the cellular distribution and biological functions of FPRs extend beyond myeloid cells and governing their activation and trafficking. In recent years, significant progress has been made to position FPRs at check points that control the resolution of inflammation, tissue repair and return to homeostasis. Accumulating data indicate a role for FPRs in an ever-increasing range of human diseases, including atherosclerosis, chronic obstructive pulmonary disease, asthma, autoimmune diseases and cancer, in which dysregulated or defective resolution are increasingly recognized as critical component of the pathogenesis. This review summarizes recent advances on how FPRs recognize distinct ligands and integrate opposing cues to govern various responses and will discuss how this knowledge could be harnessed for developing novel therapeutic strategies to counter inflammation that underlies many human diseases.