Neuronal inclusions comprised of the microtubule-associated protein tau are found in numerous neurodegenerative diseases, commonly known as tauopathies. In Alzheimer's disease - the most prevalent tauopathy - misfolded tau is probably a key pathological agent. The recent failure of amyloid-beta-targeted therapeutics in Phase III clinical trials suggests that it is timely and prudent to consider alternative drug discovery strategies for Alzheimer's disease. Here, we focus on strategies directed at reducing misfolded tau and compensating for the loss of normal tau function.