Despite the traditional view of amyotrophic lateral sclerosis (ALS) as an isolated motor neuron disorder, recent evidence suggests that ALS is, in fact, a multisystem disorder with a varying presentation and with widespread extramotor neuropathologic involvement. Support for a concept of ALS as a multisystem disorder has some basis in historical clinical reports that have highlighted the existence of a frank dementia in at least a small percentage of ALS patients. More recent evidence of extramotor involvement in ALS, derived from neurocognitive, neuropathologic, genetic, proteomic, and neuroradiologic perspectives, provides further support for these early observations and has drawn considerable attention to a possible association between ALS and frontotemporal dementia (FTD). Literature from these diverse clinical and basic scientific disciplines, when integrated, demonstrates commonalities between ALS and FTD and suggests that these disorders not only affect the same general neuroanatomic substrate, but also may represent two points on the same neuropathologic continuum. This review discusses this putative association between ALS and FTD and provides possible directions for future research in this area.