In this study, cognitive interviewing methods were used to test targeted questionnaire items from a battery of quantitative instruments selected for a large multisite trial of supported housing interventions for homeless individuals with mental disorders. Most of the instruments had no published psychometrics in this population. Participants were 30 homeless adults with mental disorders (including substance use disorders) recruited from service agencies in Vancouver, Winnipeg, and Toronto, Canada. Six interviewers, trained in cognitive interviewing methods and using standard interview schedules, conducted the interviews. Questions and, in some cases, instructions, for testing were selected from existing instruments according to a priori criteria. Items on physical and mental health status, housing quality and living situation, substance use, health and justice system service use, and community integration were tested. The focus of testing was on relevance, comprehension, and recall, and on sensitivity/acceptability for this population. Findings were collated across items by site and conclusions validated by interviewers. There was both variation and similarity of responses for identified topics of interest. With respect to relevance, many items on the questionnaires were not applicable to homeless people. Comprehension varied considerably; thus, both checks on understanding and methods to assist comprehension and recall are recommended, particularly for participants with acute symptoms of mental illness and those with cognitive impairment. The acceptability of items ranged widely across the sample, but findings were consistent with previous literature, which indicates that “how you ask” is as important as “what you ask.” Cognitive interviewing methods worked well and elicited information crucial to effective measurement in this unique population. Pretesting study instruments, including standard instruments, for use in special populations such as homeless individuals with mental disorders is important for training interviewers and improving measurement, as well as interpreting findings.