Primary 4-repeat tauopathies are neurodegenerative diseases characterized clinically by motor, oculomotor, bulbar, and cognitive deficits. Pathologically, there is accumulation of insoluble deposits of the microtubule-associated protein Tau—comprised predominantly of Tau isoforms containing four microtubule-binding domain repeats (4R-Tau)—within neurons and glia. Convergent genetic and experimental evidence suggests that 4R-Tau plays a critical role in driving pathogenesis in these diseases. Examples of primary 4R-tauopathies include sporadic diseases such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and some cases of the rare monogenic disorder FTDP-17, caused by mutations in the MAPT gene encoding Tau. Multiple different approaches have been taken to replicate the complex pathophysiology of these diseases in vertebrate animal models in vivo. These models have yielded insights into pathophysiology and provided resources for testing experimental therapeutics. Here, we review the rationale, properties, and applications of vertebrate animal models of primary 4-repeat tauopathies.