Heavy-metal (Cd, Hg, and Pb)-containing semiconductor nanocrystals (NCs) have been explored widely due to their unique optical and electrical properties. However, the toxicity risks of heavy metals can be a drawback of heavy-metal-containing NCs in some applications. Anisotropic heavy-metal-free semiconductor NCs are desirable replacements and can be realized following the establishment of anisotropic growth mechanisms. These anisotropic heavy-metal-free semiconductor NCs can possess lower toxicity risks, while still exhibiting unique optical and electrical properties originating from both the morphological and compositional anisotropy. As a result, they are promising lightemitting materials in use various applications. In this review, we provide an overview on the syntheses, properties, and applications of anisotropic heavy-metal-free semiconductor NCs. In the first section, we discuss hazards of heavy metals and introduce the typical heavymetal-containing and heavy-metal-free NCs. In the next section, we discuss anisotropic growth mechanisms, including solution−liquid−solid (SLS), oriented attachment, ripening, templated-assisted growth, and others. We discuss mechanisms leading both to morphological anisotropy and to compositional anisotropy. Examples of morphological anisotropy include growth of nanorods (NRs)/nanowires (NWs), nanotubes, nanoplatelets (NPLs)/nanosheets, nanocubes, and branched structures. Examples of compositional anisotropy, including heterostructures and core/shell structures, are summarized. Third, we provide insights into the properties of anisotropic heavy-metal-free NCs including optical polarization, fast electron transfer, localized surface plasmon resonances (LSPR), and so on, which originate from the NCs' anisotropic morphologies and compositions. Finally, we summarize some applications of anisotropic heavy-metal-free NCs including catalysis, solar cells, photodetectors, lighting-emitting diodes (LEDs), and biological applications. Despite the huge progress on the syntheses and applications of anisotropic heavy-metal-free NCs, some issues still exist in the novel anisotropic heavy-metal-free NCs and the corresponding energy conversion applications. Therefore, we also discuss the challenges of this field and provide possible solutions to tackle these challenges in the future.