Homeless individuals with co-occurring disorders (CODs) of severe mental illness and substance use disorder are one of the most vulnerable populations. This article provides practitioners with a framework and strategies for helping this client population. Four components emerged from a literature review: (1) ensuring an effective transition for individuals with CODs from an institution (such as a hospital, foster care, prison, or residential program) into the community, a particularly important component for clients who were previously homeless, impoverished, or at risk of homelessness; (2) increasing the resources of homeless individuals with CODs by helping them apply for government entitlements or supported employment (3) linking homeless individuals to supportive housing, including housing first options as opposed to only treatment first options, and being flexible in meeting their housing needs; and (4) engaging homeless individuals in COD treatment, incorporating modified assertive community treatment, motivational interviewing, cognitive-behavioral therapy, contingency management, and COD specialized self-help groups.