A new and facile method to prepare large-area silver-coated silicon nanowire arrays for surface-enhanced Raman spectroscopy (SERS)-based sensing is introduced. High-quality silicon nanowire arrays are prepared by a chemical etching method and used as a template for the generation of SERS-active silver-coated silicon nanowire arrays. The morphologies of the silicon nanowire arrays and the type of silver-plating solution are two key factors determining the magnitude of SERS signal enhancement and the sensitivity of detection; they are investigated in detail for the purpose of optimization. The optimized silver-coated silicon nanowire arrays exhibit great potential for ultrasensitive molecular sensing in terms of high SERS signal enhancement ability, good stability, and reproducibility. Their further applications in rapidly detecting molecules relating to human health and safety are discussed. A 10 s data acquisition time is capable of achieving a limit of detection of approximately 4 x 10(-6) M calcium dipicolinate (CaDPA), a biomarker for anthrax. This value is 1/15 the infectious dose of spores (6 x 10(-5) M required), revealing that the optimized silver-coated silicon nanowire arrays as SERS-based ultrasensitive sensors are extremely suitable for detecting Bacillus anthracis spores.