Abnormal protein deposits are a common feature of many human diseases including Alzheimer's disease. In Alzheimer's disease, the appearance of tangles, composed of the microtubule associated protein tau, correlates with both cell death and symptom severity. However, are tau filaments simply markers of disease progression, or are they directly responsible for cell death? Due to conflicting findings from cell and animal models, it remains controversial whether tau polymers or smaller pre-fibrillar aggregates or tau monomers are the toxic species. Indeed, if monomeric or oligomeric species are mediators of disease, formation of larger tau filaments may prove beneficial to affected cells. This review will examine the findings regarding the toxicity of various tau species.