Taddeo di Bartolo, Siena’s premier painter in the years around 1400, is the focus of a cultural history of a great Italian school in an understudied period. His patrons commissioned important fresco cycles and the most impressive polyptychs of the age. In part a travelogue, the text follows Taddeo (ca 1362-1422) from training in straitened times at Siena across central and northern Italy. Ten years of itinerancy drew him to various Tuscan centers, along the Ligurian coast from Genoa to Provence, probably to Padua, and into Umbria.  About 1399 he resettled at Siena to rapidly become the preferred painter of his commune. His mural cycles made a greater imprint on Siena’s civic iconography than has been acknowledged while his efficient Sienese shop produced outstanding panel paintings for, among others, the most dynamic religious orders. Until his last years he received grand commissions in and from beyond Siena. He drew a pope’s portrait and was employed by a cardinal at Rome. Attention to his production methods shows how his busy shop ensured variety in numerous paintings for mid-level clients by a flexible design system. Taddeo’s works, including rediscovered and reconstructed paintings, come alive in beautiful illustrations. This chronicle of an indefatigable and successful late medieval career positions the painter, his colleagues, and his patrons in their political, economic, and social circumstances. It provides new insights on Siena’s artistic culture at the start of the Renaissance.