Many properties of single-walled carbon nanotubes (SWCNTs) make them ideal candidates for sensors, particularly for biological systems. Both their fluorescence in the near-infrared range of 820–1600 nm, where absorption by biological tissues is often minimal, and their inherent photostability are desirable attributes for the design of in vitro and in vivo sensors. The mechanisms by which a target molecule can selectively alter the fluorescent emission include primarily changes in emission wavelength (i.e., solvatochromism) and intensity, including effects such as charge-transfer transition bleaching and exciton quenching. The central challenge lies in engineering the nanotube interface to be selective for the analyte of interest. In this work, we review the recent development in this area over the past few years, and describe the design rules that we have developed for detecting various analytes, ranging from stable small molecules and reactive oxygen species (ROS) or reactive nitrogen species (RNS) to macromolecules. Applications to in vivo sensor measurements using these sensors are also described. In addition, the emerging field of SWCNT-based single-molecule detection using band gap fluorescence and the recent efforts to accurately quantify and utilize this unique class of stochastic sensors are also described in this article.