Two-way shape memory polymers (2W-SMPs) are a novel class of shape memory polymers with the reversible and programmable shape-changing behavior which have gained considerable attention compared to one-way shape memory polymers (1W-SMP). Although several promising polymers have been developed to exhibit two-way shape memory effect and there are a number of reviews discussing the general concepts of shape memory polymers, the focus has been attributed to 1W-SMPs. A review focusing on only 2W-SMPs structure, mechanism, and application is still lacking. Herein, a comprehensive review focusing on 2W-SMPs structures, mechanisms, and applications is presented. This review will also emphasize on future insight of 2W-SMPs as an independent theme. The molecular strategies of 2W-SMPs, liquid crystalline elastomers, semi-crystalline networks, composites and interpenetrating networks are thoroughly discussed. Molecular mechanisms attributed to net-points, switching segments, and entropic energy changes are also explained. Considerable efforts have been devoted to explore the underlying mechanisms and strategies of 2W-SMPs in response to different stimulations, enabling their applications in emerging fields including biomedical engineering, aerospace and electronics.