Alzheimer’s disease (AD) is characterized by cognitive impairment that starts with memory loss to end in dementia. Currently the major hallmarks in AD pathogenesis are soluble oligomers of Aβ peptide, which derive from the processing of APP protein and are responsible for synapses loss and cognitive impairment and accumulation of hyperphosphorylated tau. Several kinases are involved in these pathological processes; amongst them JNK is activated in human AD brains, and associated with the development of memory deficits and long-term potentiation (LTP) impairment. Interestingly JNK mediates phosphorylation of APP in Thr-668, inducing its amyloidogenic cleavage and the formation of soluble Aβ oligomers. Moreover JNK contributes to tau hyperphosphorylation at S202/T205 and S422. Finally recent evidences suggested that JNK phosphorylates PSD-95 controlling its level at the post-synaptic density and consequently participates to synaphopathy. By regulating the described key pathogenic mechanisms of AD, JNK might hold promise as an innovative therapeutic target.