The 2003 pandemic of Severe Acute Respiratory Syndrome (SARS) profiled the ability of modern diagnostic microbiology and molecular biology to identify, isolate and characterize, within weeks, a previously unknown viral infectious pathogen. The culprit, SARS coronavirus (SARS-CoV), was detected in patient specimens by traditional cell culture using an unusual cell line for respiratory viruses, Vero E6, and by reverse transcriptase polymerase chain reaction (RT-PCR) targeting the polymerase 1 B region of the genome. In addition, serologic assays were rapidly developed, and the genome of this large virus was sequenced within one month of its spread to North America. At the present time, diagnostics have progressed to the point that RT-PCR has a sensitivity approaching 80% within the first few days of onset of illness, while serology has a sensitivity close to 100% on convalescent sera taken >21 days after illness onset. Viral culture remains a method confined to biosafety level III laboratories. The specificity of RT-PCR and serology remains to be conclusively defined, but in most studies to date seems to be >90%. Serologic cross-reactivity with human coronaviruses causing the common cold may be a problem with some serologic assays. The early development of SARS-CoV diagnostics is now being replaced by refinement and optimization of these assays. Although at the present time we do not have a test that will definitively rule in or rule out SARS at the time of initial presentation of a patient with a respiratory infection, modifications of existing assays will hopefully result in our ability to make this diagnosis with a high degree of accuracy in the future.