The quantification and detection of biochemical species are of utmost importance for biomedical applications. Silicon nanowire field-effect transistors (SiNW-FETs) have recently attracted tremendous attention as a promising tool in biosensor design because of their ultrahigh sensitivity, selectivity, and label-free and real-time detection capabilities. Here, we review the device fabrication and biomedical applications of SiNW-FET sensors. CMOS-compatible approaches for SiNW fabrication are reported. The applications of SiNW-FETs in the fields of biomedical sciences are discussed. SiNW-FETs have been employed in the detections of, for example, pH, DNA, nucleic acid, proteins, and cancer biomarkers. The major limitations and future directions of SiNW-FET nanosensors are also discussed. In this paper, we clearly show the great potential of SiNW-FET devices as powerful new tools in biological and medical diagnostics.