Polythiophenes (PTs) are one of the most important classes of conjugated polymers employed as semiconductors in organic field-effect transistors (OFETs). In the last few years, versatile thiophene-based polymers have received great interest for applications in large-area, flexible, and low-cost electronics attributing to their excellent optoelectronic properties. Significant progress has been made in PT-based semiconductors for high performance transistors. We review here the achievements gained in conjugated PT-based semiconductors and demonstrate their structural modifications and design principles. We highlight the most important semiconducting polymers created from PT derivatives obtained through rational monomer design, controlled π-conjugation and appropriately positioned pendant side-chain distribution. Finally, we discuss remaining challenges and outline our views on future developments.