Recently dark-field microscopy and Rayleigh scattering spectroscopy have emerged as complementary technologies for ultrasensitive biological detection and imaging with high spatial and temporal resolution. Plasmonic resonant nanoparticles are key nano-scale probes for these technologies that have enabled single-molecule sensitivity and imaging. In this tutorial review, we focus on the use of plasmonic probes as single-particle biological nanosensors in vitro and in vivo. The progress in this field over the last decade will be highlighted.