Perfectly aligned arrays of single-crystalline silicon nanowires were fabricated using top-down CMOS-compatible techniques. We demonstrate that these nanowire devices are able to detect adipocytokines secreted by adipose cells with femtomolar sensitivity, high specificity, wide detection range, and ability for parallel monitoring. The nanowire sensors also provide a novel tool to reveal the poorly understood signaling mechanisms of these newly recognized signaling molecules, as well as their relevance in common diseases such as obesity and diabetes. © The Royal Society of Chemistry 2009.