Severe acute respiratory syndrome (SARS) is a newly found infectious disease that is caused by a novel human coronavirus, SARS coronavirus (SARS-CoV). Because the mortality rate of SARS patients is very high, understanding the pathological mechanisms of SARS not only in vivo but in vitro is important for the prevention of SARS. Activation of signaling pathways caused by SARS-CoV infection leads to the phosphorylation and activation of downstream molecules. Two conflicting cellular programs, apoptosis to eliminate virus-infected cells and survival to delay apoptosis by producing antiviral cytokines, occur in SARS patients. Recent studies regarding SARS and SARS-CoV have clarified that activation of mitogen-activated protein kinases (MAPKs) plays important roles in upregulation of cytokine expression and apoptosis both in vitro and in vivo. Both Akt and p38 MAPK are keys for determination of cell survival or death in SARS-CoV-infected cells in vitro. Agents being developed to target these signaling cascades may be important for the design of anti-SARS-CoV drugs. This review highlights recent progress regarding SARS-CoV biology, especially signal transduction in SARS-CoV-infected cells.