Nanowire field effect transistors (NWFETs) are emerging as powerful sensors for bio-molecule detection. I will discuss the interplay of device parameters such as gate bias and NW diameter on the sensitivity of NWFET sensors. Based on a fundamental understanding of the device physics, we demonstrate greatly improved sensitivity in both pH and cancer marker protein detections by operating the NWFET in the subthreshold regime where carriers in nanowire have reduced screening ability.