Healthcare workers (HCWs) in low- and middle-income countries with high tuberculosis prevalence are at increased risk of tuberculosis infection; however, tuberculosis infection control (TBIC) measures are often poorly implemented. The World Health Organization recommends 4 levels of TBIC: managerial (establishment and oversight of TBIC policies), administrative controls (reducing HCWs’ exposure to tuberculosis), environmental controls (reducing the concentration of infectious respiratory aerosols in the air), and personal respiratory protection. This article will discuss each of these levels of TBIC, and review the available data on the implementation of each in sub-Saharan African countries. In addition, we review the attitudes and motivation of HCWs regarding TBIC measures, and the impact of stigma on infection control practices and implementation. After summarizing the challenges facing effective TBIC implementation, we will discuss possible solutions and recommendations. Last, we present a case study of how a clinic effectively addressed some of the challenges of TBIC implementation.