Background To evaluate function and disability, the WHO has developed the WHO Disability Assessment Schedule II (WHODASII), an instrument arising from the same conceptual basis as the International Classification of Functioning, Disability, and Health (ICF). Objectives The general objective of this study was to investigate whether the WHODASII--German version--is a valid instrument to measure functioning and disability across various conditions. Specific aims were (1) to assess its psychometric properties (reliability, validity, and sensitivity to change) based on the traditional test theory and (2) to compare its sensitivity to change after a rehabilitative intervention to the Short Form 36 (SF-36). Research design This was a multi-center study with convenience samples of patients with different chronic conditions undergoing rehabilitation. Patients completed the WHODASII and the SF-36 before and after a rehabilitation treatment. Health professionals rated in cooperation with the patients the pain of the patients based on the ICF category "sensation of pain." Results 904 patients were included in the study. The Cronbach's range from 0.70 to 0.97 for the different subscales of WHODASII. With exception of the subscale Activities, the exploratory-factor structure of the WHODASII corresponds highly with the original structure. The effect size (ES) of the WHODASII total score ranged from 0.16 to 0.69 depending on the subgroup. The ES of the SF-36 summary scores ranged from 0.03 to 1.40. Conclusions The WHODASII (German version) is a useful instrument for measuring functioning and disability in patients with musculoskeletal diseases, internal diseases, stroke, breast cancer, and depressive disorder. The results of this study support the reliability, validity, dimensionality, and responsiveness of the German version of the WHODASII. However, the reproducibility in test-retest samples of stable patients, as well as the question to what extent a summary score can be constructed, requires further investigation.