A hallmark pathological feature of Alzheimer's disease (AD) is the accumulation of extracellular plaques composed of the amyloid-beta (Aβ) peptide. Thus, classically experiments were designed to examine Aβ toxicities within the central nervous system (CNS) from the extracellular space. However, a significant amount of evidence now suggests that intraneuronal accumulation of Aβ is neurotoxic and may play an important role in the disease progression of AD. One of the means by which neurons accumulate intracellular Aβ is through uptake of extracellular Aβ peptides, and this process may be a potential link between Aβ generation, synaptic dysfunction, and AD pathology. Recent studies have found that neuronal internalization of Aβ involves lipid rafts and various lipid raft-associated receptor proteins. Uptake mechanisms independent of lipid rafts have also been implicated. The aim of this paper is to summarize these findings and discuss their significance in the pathogenesis of AD.