Context: People living with human immunodeficiency virus (HIV) (PLWH) who are most at risk for falling out of HIV primary care and detectable viral loads include homeless and unstably housed individuals and those codiagnosed with behavioral health disorders. The patient-centered medical home (PCMH) is a model that promotes provision of comprehensive, patient-centered, accessible, coordinated, and quality care for patients. This initiative provided patient navigation to HIV-positive homeless and unstably housed individuals codiagnosed with a mental health or substance use disorder as a means to create an adapted PCMH to meet the specific needs of this population. Objective: The purpose of this analysis was to characterize the roles and responsibilities of patient navigators as part of an effort to create a medical home for homeless and unstably housed PLWH with behavioral health comorbidities. Design: Eighty-one in-depth interviews with clinic staff and 2 focus groups with patient navigators were conducted. Content analysis was performed to identify key roles and responsibilities of the patient navigators. Results: Patient navigators played an important role in creating a PCMH by working with clients to schedule and complete appointments, develop comprehensive care plans, forging critical relationships with providers both within and outside of health care systems, providing holistic support to increase patient self-management, and assisting in achieving housing stability. Conclusions: It may be necessary to adapt the traditional PCMH model to effectively meet the social, behavior health, and medical needs of homeless and unstably housed PLWH with behavioral health comorbidities. A patient navigator who can invest time in supporting and connecting these patients to needed services may be a key component in creating an effective PCMH for this population. These findings highlight the roles and tasks of patient navigators that may contribute to developing a PCMH specific to homeless and unstably housed PLWH with mental health and substance use comorbidities. Implementation of such a model has the potential to improve health outcomes (such as retention in care and viral suppression) for particularly vulnerable PLWH and thereby reduce the burden of HIV infection.