During the past few decades, most fluorescent materials generated photoluminescence (PL) signals in the visible (400-650 nm) and the first near-infrared (NIR-I) region (650-950 nm). On the other hand, the second near-infrared (NIR-II) window (10001700 nm) has shown the merits of high signal-tobackground ratios (SBRs) and optical resolutions at depths because of reduced interface reflection, autofluorescence, and photon scattering. Many inorganic NIR-II fluorescent materials have been developed with narrow emission bands and high photostability. However, their applications are still impeded by inevitable drawbacks like low quantum yields (QYs), poor reproducibility, and high toxicity. Organic small molecules with NIR-II emission are potential candidates for bioimaging because of good biocompatibility, well-defined molecular structures, and ease of synthetic modification. To red-shift the emission wavelength of NIR-II dyes, two strategies are commonly used. The first strategy is to enlarge the conjugation length. However, it cannot always work practically because of tedious synthesis, unsatisfactory processability, and instability (especially for cyanine dyes with extended double bonds). Another strategy is to design dyes with donoracceptor (D-A) structures rationally. The D-A strategy can effectively reduce the band gaps through relatively simple synthesis. Unfortunately, the QYs of NIR-II dyes are always extremely low in practical usage. This phenomenon is believed to result from: (1) Most dyes with long-wavelength emission adopt extensively conjugated backbones, and the resultant strong intermolecular interactions may easily cause aggregation-caused quenching (ACQ) effects in concentrated solutions or the aggregate state. (2) The D-A interactions are normally strong, which may cause severe twisted intramolecular charge transfer (TICT) to weaken the emission in polar environments. (3) The band gaps are incredibly narrow, so the formed excitons can easily undergo non-radiative decay pathways by molecular motions. These problems severely retarded the development of NIR-II dyes for bioimaging because the physiological environment is an aqueous medium, where the hydrophobicity of the molecules and the high polarity of the environment can cause an even worse fluorescence quenching effect.