Alzheimer's disease is a chronic neurodegenerative devastating disorder affecting a high percentage of the population over 65 years of age and causing a relevant emotional, social, and economic burden. Clinically, it is characterized by a prominent cognitive deficit associated with language and behavioral impairments. The molecular pathogenesis of Alzheimer's disease is multifaceted and involves changes in neurotransmitter levels together with alterations of inflammatory, oxidative, hormonal, and synaptic pathways, which may represent a drug target for both prevention and treatment; however, an effective treatment for Alzheimer's disease still represents an unmet goal. As neurotrophic factors participate in the modulation of the above-mentioned pathways, they have been highlighted as critical contributors of Alzheimer's disease etiology, whose modulation might be beneficial for Alzheimer's disease. We focused on the neurotrophin brain-derived neurotrophic factor, providing several lines of evidence pointing to brain-derived neurotrophic factor as a plausible endophenotype of cognitive deficits in Alzheimer's disease, illustrating some of the most recent possibilities to modulate the expression of this neurotrophin in the brain in an attempt to ameliorate cognition and delay the progression of Alzheimer's disease. This review shows that otherwise disparate pharmacologic or non-pharmacologic approaches converge on brain-derived neurotrophic factor, providing a means whereby apparently unrelated medical approaches may nevertheless produce similar synaptic and cognitive outcomes in Alzheimer's disease pathogenesis, suggesting that brain-derived neurotrophic factor-based synaptic repair may represent a modifying strategy to ameliorate cognition in Alzheimer's disease.