A recent resurgence of tuberculosis (TB) has been driven mostly by the HIV epidemic. The initial inpatient experience for individuals with HIV-related TB may be pivotal to the acceptance of and participation in ongoing TB care. The purpose of this study was to develop an understanding of the experience of respiratory isolation for HIV-infected patients with TB in order to identify strategies for enhancing quality of life and participation in care. Respondents (N = 18) identified 12 major themes related to the isolation and reported more mood disturbances during their confinement than the norm. This study suggests that staff behaviors which foster human connections may enhance the patient's quality of life and promote adherence to therapy.