Knowledge of the mechanical properties of organic semiconductors is critical for the long-term stability of flexible devices fabricated using roll-to-roll printing techniques. Moreover, increasing the elastic range and resistance to fracture of these materials will enable stretchable and ultra-flexible devices for portable, wearable, implantable, and disposable applications. Despite the importance of the mechanical properties of low-bandgap (i.e., donor-acceptor) conjugated polymers, there are no design rules available that have the goal of maximizing the charge transport properties along with the mechanical deformability. This talk describes my group’s experimental and theoretical approaches to understanding the molecular and microstructural determinants of the mechanical properties of these materials. Our approach began with the measurement of a large library containing over 50 donor-acceptor conjugated polymers. Among the design rules that emerged from this study is the importance of (1) branched side chains and (2) isolated rings (e.g., bithiophene) as opposed to fused rings (e.g., thienothiophene) along the backbone. To obtain a deeper understanding of these properties, we are developing a coarse-grained molecular dynamics approach to determine the glass transition temperature, elastic moduli, Poisson ratio, and toughness of a representative subset of these materials. Among our findings are that the density of entanglements, which critically determines the fracture energy and toughness, is highly dependent on the conformation of the chains in solution prior to deposition. Finally, we describe the first study of the mechanical properties of solution-processed small-molecule semiconductors. These materials exhibit a surprisingly high ductility in pure form, with some films able to withstand ≥10% tensile strain without fracture.