The basal forebrain region includes a large group of cholinergic neurons within the medial septal area and nucleus basalis magnocellularis (NBM) that project to the hippocampus and throughout the neocortex, respectively. This chapter will consider the mechanisms that influence why cholinergic cells within the NBM die and discuss studies that have manipulated the features of these cells that could make them differentially vulnerable to degeneration with aging and Alzheimer's Disease (AD). This chapter will focus upon the NBM cholinergic system because this regions typically demonstrates a greater degree of cell loss with aging and AD.