Conjugated polymers are promising candidates for next-generation low-cost flexible electronics. Field-effect transistors comprising conjugated polymers have witnessed significant improvements in device performance, notably the field-effect mobility, in the last three decades. However, to truly make these materials commercially competitive, a better understanding of charge-transport mechanisms in these structurally heterogeneous systems is needed for providing systematic guides for further improvements. This review assesses the key microstructural features of conjugated polymers across multiple length scales that can influence charge transport, with special attention given to the underlying polymer physics. The mechanistic understanding from collective experimental and theoretical studies point to the importance of interconnected ordered domains given the macromolecular nature of the polymeric semiconductors. Based on the criterion, optimization to improve charge transport can be broadly characterized by efforts to (a) promote intrachain transport, (b) establish intercrystallite connectivity, and (c) enhance interchain coupling. (c) 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019