<p>The emerging concept of single-atom catalysts (SACs) has rapidly devolved from its inception to widespread development in just over a decade, reflecting the consensus among researchers regarding their immense application potential. SACs enable efficient, environmentally friendly, and sustainable catalytic synthesis through precise modulation of the support, metal atoms, and their interactions. More importantly, the novel catalytic mechanisms they exhibit, which differ from traditional homogeneous catalysis, are highly exciting. This review summarizes recent advances in the application of SACs, a highly promising strategy, in the field of organic synthesis. By discussing mechanisms and emphasizing the critical roles of SACs that differentiate them from conventional metal catalysts, we aim to provide a comprehensive understanding of their unique advantages. Finally, we outline the opportunities, challenges, and future directions for SACs in organic synthesis.</p>