There is an overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Some 5-10% of ALS patients show changes in their behaviour and personality that are characteristic of FTD and about 10% of FTD patients develop ALS. Mild cognitive impairment occurs in 30% of ALS patients. The progressive decline of muscle strength in ALS patients and social skills in FTD patients places severe demands on the patient and his or her contacts. In some ALS and FTD patients, ubiquitin-positive inclusions have been found in the hippocampus and anterior horn cells. In patients with familial FTD who have ubiquitin-positive inclusions, mutations have been found in the progranulin (PGRN) gene. TAR-DNA-binding protein-43, encoded by the TARDBP gene, has recently been identified as a constituent of the ubiquitin inclusions. TARDBP and PGRN mutations are found in patients with ALS. The overlapping characteristics provide clues for further research into the pathogenesis of ALS and FTD.