It is important not only to monitor the functional change during the course of ALS, but also to determine whether or not the available help is sufficient. This study was performed to determine which generic assessment instrument is most appropriate. A multicentre cohort of patients with ALS was followed for one year. At baseline, six months, and 1 year four instruments were used: Functional Independence Measure (FIM), Rehabilitation Activities Profile (RAP), Barthel Index (BI), and Frenchay Activities Index (FAI). The responsiveness of the measures was examined using effect sizes and standardized response mean statistics. Seventy-three patients at baseline, 63 after six months and 43 after one year were assessed. If calculated on the group that completed all three assessments, the FIM, BI, and RAP showed moderate effect sizes and standardized response means over a period of six months and large effect sizes over 12 months. Based on their responsiveness FIM, BI, and RAP can be used to evaluate limitations in activities and care needs of persons with ALS and to evaluate treatment results in trials. The FIM was the most responsive instrument, although the BI might be easier to use in clinical practice.