The amyloid-beta peptide cascade hypothesis has provided a useful framework for the research on Alzheimer's disease for nearly 20 years. According to this hypothesis, an increase in amyloid-beta levels triggers all of the pathological features of the disease, including tau hyperphosphorylation, appearance of neurofibrillary tangles, synaptic dysfunction and neuronal cell death. Even though amyloid-beta peptide has an important role in the neurodegenerative process, different findings, such as the presence of abundant plaques in old cognitively normal individuals or the limited success of therapeutical approaches targeting only amyloid-beta, cast some doubt on a unique role for this peptide. At present, it is rather accepted that amyloid-beta peptide acts in parallel with other factors causing Alzheimer's disease that should be also considered at the time of designing useful therapeutic strategies.