The maintenance of intracellular trafficking is essential to neuron survival. Well-organized intracellular events contribute to synapse effectiveness and efficient communication between cells. Changes in microtubule trackers, vesicles, mitochondria or autophagosomes can lead to neurodegeneration. Protein aggregates containing amyloid-beta peptides and hyperphosphorylated tau are hallmarks of Alzheimer’s disease and they impair intracellular trafficking. Moreover, dysfunction of intracellular transport might increase the formation of protein aggregates. In this chapter it is discussed the association between intracellular trafficking and Alzheimer’s disease with emphasis in protein aggregation, cholesterol transport, molecular motors, rab proteins, autophagy, endoplasmic reticulum, mitochondria and calcium homeostasis.