With more than two-thirds of utilized energy being lost as waste heat, there is compelling motivation for high-performance thermoelectric materials that can directly convert heat to electrical energy. However, over the decades, practical realization of thermoelectric materials has been limited by the hitherto low figure of merit, ZT, which governs the Carnot efficiency. This article describes our long-standing efforts to advance ZT to record levels starting from exploratory synthesis and evolving into the nanostructuring and panoscopic paradigm, which has helped to usher in a new era of investigation for thermoelectrics. The term panoscopic is meant as an attempt to integrate all length scales and multiple physical concepts into a single material. As in any other energy-conversion technology involving materials, thermoelectrics research is a challenging exercise in taming “contra-indicated” properties. Critical properties such as high electrical conductivity, thermoelectric power, low thermal conductivity, and mechanical strength do not tend to favor coexistence in a single material. How these can be achieved in certain systems leading to record values of ZT is also described. Endotaxial nanostructures and mesoscale engineering in thermoelectrics enable effective phonon scattering with negligible electron scattering. By combining all relevant length scales hierarchically, we can achieve large enhancements in thermoelectric performance. The field, however, continues to produce surprises.