Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) are two frequent forms of primary neurodegenerative dementias. Despite distinctive clinical diagnostic criteria for both brain disorders, differential diagnosis is often complicated by overlapping symptomatology. As we learn more about brain pathology and genetic makeup underlying these dementia disorders, evidence is accumulating for a clinical, pathologic, and genetic spectrum of neurodegenerative brain diseases in which AD and FTLD occur along one continuum. This has important implications for molecular diagnostic testing and genetic counseling of patients with dementia. In this light, we review the molecular genetics of AD and FTLD assessing how AD genes can be implicated in FTLD and conversely FTLD genes in AD, by modifying disease susceptibility. Herein, we focus on recent exciting findings providing further support for an AD-FTLD spectrum.