In molecular neurobiology, perhaps no molecule has been as thoroughly examined as Alzheimer's ß-amyloid precursor protein (ßAPP). In the ten years since the cDNA encoding ßAPP was cloned, the protein has been the subject of unparalleled scrutiny on all levels. From molecular genetics and cellular biology to neuroanatomy and epidemiology, no scientific discipline has been left unexplored - and with good reason. ß-amyloid (Aß) is the main constituent of the amyloidogenic plaques which are a primary pathological hallmark of Alzheimer's disease, and ßAPP is the protein from which Aß is cleaved and released. Unraveling the molecular events underlying Aß generation has been, and remains, of paramount importance to scientists in our field. In this review we will trace the progress that has been made in understanding the molecular and cellular basis of ßAPP trafficking and processing, or alternatively stated, the molecular basis for Aß generation. Imperative to a complete understanding of Aß generation is the delineation of its subcellular localization and the identification of proteins which play either direct or accessory roles in Aß generation. We will focus on the regulation of ßAPP cleavage through diverse signal transduction mechanisms and discuss possible points of therapeutic intercession in what has been postulated to be a seminal molecular step in the cascade of events terminating in the onset of dementia, a loss of neurons, and tragically, eventual death from Alzheimer's disease.