Unfortunately, no drug treatment has been shown to benefit patients with progressive supranuclear palsy (PSP) more than modestly or briefly. The multiplicity of neuronal systems and synaptic physiologies that degenerate in this disorder makes a neurotransmitter-specific approach, such as neurotransmitter replacement or reuptake inhibition, unlikely to succeed. Nevertheless, some of these are worth trying in nearly every patient with PSP. Useful drug treatment may ultimately take the form of enhancers of mitochondrial energy metabolism, inducers of endogenous neurotrophic factors, and, even further in the future, inhibitors of tau aggregation or regulators of alternative splicing. The neurologist familiar with PSP can assist patients and their family by providing prognostic information, by avoiding unnecessary diagnostic tests, and by prescribing measures to minimize aspiration and falling, the two most dangerous complications of PSP.