Abstract An urban shelter in Charleston, South Carolina developed and began a tuberculosis (TB) prevention and control plan that addressed the priorities recommended by the Centers for Disease Control and Prevention. After an increase in TB in the shelter in 1992, the local health department, the homeless clinic nurse practitioners, and Medical University of South Carolina College of Nursing faculty and students collaborated with the shelter staff to provide initial mass screenings for contact investigation. They also developed and implemented new policies and procedures for an ongoing TB prevention and control program. The new policies required that guests obtain screening for TB within 7 days of arrival at the shelter and every 6 months thereafter. Also, a public health nurse began providing directly observed therapy twice weekly at the shelter. Of the initial 22 persons who started TB preventive therapy in 1993, 17 (77%) completed therapy. The clinic nurse practitioners, nursing students, and public health nurses had important and defined roles in the mass-screening process, case identification and treatment, policy development and implementation, health education, and establishing methods of communication between the shelter, clinic, and health department. An ongoing health care community collaborative effort may successfully reduce tuberculosis disease in a homeless shelter population.