Context. Quality of life (QOL) for patients is now a worldwide concern, but there are few specific instruments developed by modular approach to measure outcomes in chronic diseases. Objectives. This study aimed to develop and validate the System of Quality of Life Instruments for Chronic Diseases-General Module (QLICD-GM). Methods. Based on the World Health Organization's definition of QOL and programmed decision procedures, the QLICD-GM was developed using focus group discussions, pilot tests of 201 cases, and field tests of 620 cases representing seven different chronic diseases. The number of items in the final version was reduced to 30 from a 73-item pool, and the psychometric properties of the scale were evaluated by indicators, such as validity and reliability coefficients, standardized response mean, and statistical methods of correlational analysis, t-tests, and structural equation modeling. Results. Correlational and structural equation model analyses confirmed good construct validity with root mean square error of approximation of 0.0606, nonnormed fit index of 0.941, and comparative fit index of 0.947. Test-retest reliability coefficients for all domains and facets were higher than 0.70, with a range of 0.71-0.92, and the internal consistency alphas for most domains and facets were higher than 0.65 (ranging from 0.52 to 0.89). All domains and overall scores of the QLICD-GM had a statistically significant change after treatment, with moderate effect size. Conclusion. The QLICD-GM has good validity, reliability, and better responsiveness compared with the SF-36 (R) Health Survey and can be used as the general module for chronic diseases. J Pain Symptom Manage 2011; 42: 93-104. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.