Paullones constitute a new family of benzazepinones with promising antitumoral properties. They were recently described as potent, ATP‐competitive, inhibitors of the cell cycle regulating cyclin‐dependent kinases (CDKs). We here report that paullones also act as very potent inhibitors of glycogen synthase kinase‐3β (GSK‐3β) (IC₅₀: 4–80 nm) and the neuronal CDK5/p25 (IC₅₀: 20–200 nm). These two enzymes are responsible for most of the hyperphosphorylation of the microtubule‐binding protein tau, a feature observed in the brains of patients with Alzheimer’s disease and other neurodegenerative ‘taupathies’. Alsterpaullone, the most active paullone, was demonstrated to act by competing with ATP for binding to GSK‐3β. Alsterpaullone inhibits the phosphorylation of tau in vivo at sites which are typically phosphorylated by GSK‐3β in Alzheimer’s disease. Alsterpaullone also inhibits the CDK5/p25‐dependent phosphorylation of DARPP‐32 in mouse striatum slices in vitro. This dual specificity of paullones may turn these compounds into very useful tools for the study and possibly treatment of neurodegenerative and proliferative disorders.