ConspectusThe growing energy crisis and the adverse environmental impacts caused by carbon-based energy consumption have spurred the exploration of green and sustainable energy. Researchers have been devoted to developing thermoelectric technology that could directly and reversibly convert heat into electricity. By virtue of zero emissions, nonmoving parts, precise temperature control, and long service life, thermoelectrics exhibit broad application in power generation and refrigeration. Nevertheless, traditional narrow-bandgap thermoelectrics exhibit high performance within a narrow temperature range, limiting the overall energy conversion. Consequently, a selection rule for exploring advanced thermoelectrics was proposed: materials with wide-bandgap, crystals form, asymmetry, and anisotropic structure. According to the rules, we conducted much research and found some promising materials.As the lead-free, cost-effective, and stable thermoelectric candidates, layered SnSe crystals with wide-bandgap and covalent bonding have gained significant attention due to their ultralow thermal conductivity resulting from strong bonding anharmonicity, via strong polar covalent bonding, because of the electronegativity difference between the Sn and Se atoms. This was proved to be the result from the unique structure of layered SnSe crystals, a distorted rock-salt structure with high and anisotropic Grüneisen parameters. In this Account, we introduce and rethink our recent advancements in developing high-performance thermoelectric SnSe crystals from computational materials science, involving p- and n-type SnSe crystals, respectively. For p-type SnSe crystals, according to the complex valence band structures, we utilized the multiband synglisis via electronic structure calculations and multiband simulations to activate valence bands to participate in electrical transport of in-plane direction, achieving an ultrahigh power factor (PF) of ∼75 μW cm-1 K-2 at room temperature and an average figure-of-merit ZTave of ∼1.9 for Sn0.91Pb0.09Se. Besides, on the basis of defect chemistry, the characteristics of p-type SnSe crystals are determined by intrinsic Sn vacancies. We thus used point-defect calculations to achieve the lattice plainification, and we fixed the lattice intrinsic defects to weaken defect scattering of carriers along the in-plane direction, facilitating further a PF > 100 μW cm-1 K-2 and a ZT of ∼1.5 at room temperature for SnCu0.001Se. For n-type SnSe crystals, inspired by the anisotropic characteristics of the layered materials, we analyzed charge density and proposed the insight of 3D charge and 2D phonon transports and calculated the deformation potential to manipulate layered phonon-electron decoupling to achieve high performance, ultimately Pb-alloyed and Cl-doped SnSe (SnSe-Cl-PbSe) reaching a ZTave of ∼1.7 from 300 to 773 K. In the end, we offer potential perspectives on high-throughput calculations (HTC) and machine learning (ML), combined with our proposed insights, which could be a promising avenue for future thermoelectrics. By virtue of our theoretical and experimental understanding of thermoelectrics, integrating these insights as rules and descriptors for HTC and ML will accelerate the research and development of thermoelectrics. We want to share our recent works and latest perspectives in SnSe thermoelectrics, and we expect to inspire enthusiasm for innovative research on advanced thermoelectric materials and devices.