The aligned silver nanorod array substrates prepared by the oblique angle deposition method are capable of providing extremely high enhancement factors (∼ 5 × 108) at near-infrared wavelengths (785 nm) for a standard reporter molecule 1,2 trans-(bis)pyridyl-ethene (BPE). The enhancement factor depends strongly on the length of the Ag nanorods, the substrate coating, the polarization of the excitation light, as well as the incident angle. With the current optimum structure, we demonstrate that the detection limit for BPE can be lower than 0.1 fM. We also show that this surface-enhanced Raman spectroscopy (SERS)-active substrate can serve as a sensor to detect and differentiate the molecular fingerprints of several important human pathogens, particularly, respiratory syncytial virus, human immunodeficiency virus, rotavirus, and the bacterium Mycoplasma pneumoniae. Utilizing chemometric methods, SERS nanorod array data can be used to sensitively detect and to classify viruses at the strain level. These results suggest that the SERS Ag nanorod array is a powerful technique for direct, rapid, and sensitive detection of infectious agents. © 2008 IEEE.