Sphingosine-1-phosphate (S1P) is a lysophospholipid signaling molecule that regulates important biological functions in both intracellular and extracellular compartments.  It interacts with five G protein-coupled receptors subtypes (S1PR₁₋₅) to generate multiple downstream signaling.  Activation of S1PR₁ has been validated to be involved in the process of immune modulation.  Fingolimod (FTY720), the novel S1PR₁ agonist, has been approved for the treatment of multiple sclerosis in clinical trials.  The study towards discovery of selective S1PR₁ agonists has become hot spot for immunological diseases.  This article summarized the research progress of S1PR₁ agonists, emphasizing their structure types, structure-activity relationship and direction of development.