In the past 10 years, two respiratory viral infections-severe acute respiratory syndrome (SARS) and H5N1-have emerged that have led to a high mortality among infected individuals. Laboratory investigations have demonstrated that these two emerging infections have similar features; and understanding the pathophysiological mechanisms of the disease causation will lead to insight into standard and novel treatments for these infections. In this review we highlight the similarities and differences of SARS and H5N1, and emphasize the importance of appropriate sampling for laboratory diagnosis of the latter.