Cytokine storm defines a dysregulation of and an excessively exaggerated immune 
response most often accompanying selected viral infections and several 
autoimmune diseases. Newly emerging and re-emerging infections of the 
respiratory tract, especially influenza, SARS, and hantavirus post considerable 
medical problems. Their morbidities and mortalities are often a direct result of 
cytokine storm. This chapter visits primarily influenza virus infection and 
resultant cytokine storm. It provides the compelling evidence that illuminates 
cytokine storm in influenza pathogenesis and the clear findings that cytokine 
storm is chemically tractable by therapy directed toward sphingosine-1-phosphate 
receptor (S1PR) modulation, specifically S1P1R agonist therapy. The mechanism(s) 
of how S1P1R signaling works and the pathways involved are subjects of this 
review.