Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the predominant form of dementia. Since its initial description by Alois Alzheimer in 1906, several advances have been made in our understanding of the progression of the disease and its clinical consequences, yet the underlying etiology remains contentious. Given the stereotyped patterns of cortical and hippocampal neuronal loss and the progressive degeneration of key neurotransmitter pathways, research has traditionally been focused on factors affecting neuronal viability, including the contribution of glial dysfunction to neuronal degeneration. From a clinical perspective, the fruits of this work have been underwhelming. Key pathological markers of the disease, including β-amyloid (Aβ) plaque formation and tau hyperphosphorylation, have yielded no effective therapies, highlighted by the recent discontinuations of several high profile Aβ immunotherapy trials. The few current symptomatic therapies for AD are predicated on the amelioration of cholinergic or glutamatergic dysfunction. Aside from underscoring the inadequacy of current therapeutic approaches, this also points to the importance of alternative contributors to AD pathogenesis. In recent years, there has been a growing appreciation for the multimodal and multifactorial nature of the condition; the case for combinatorial therapies is thus strong.