Development of fluorophores with emission in the so‐called second near‐infrared window (NIR‐II, 1000–1700 nm) represents an active area of the contemporary research. Among the available NIR‐II fluorophores, semiconductor nanocrystals are attractive owing to their high brightness, broad excitation profile, easily adjustable emission wavelength, and superior stability. At the same time, for the biomedical applications, biocompatibility of semiconductor nanocrystals is yet another important requirement. The recent advances in the synthesis of NIR‐II emitting semiconductor nanocrystals based on I‐VI, III‐V, and I‐III‐VI compound semiconductors are reviewed, placing special emphasis on the efforts to enhance their NIR‐II emission intensity and photostability. Representative examples of their applications for biomedical imaging, therapy and surgery are provided. This review is concluded by offering perspectives on how to further improve the performance of these attractive class of NIR‐II fluorophores.