Central line-associated bloodstream infections (CLABSIs) are considered a significant cause of mortality in hospitalized patients; however, the incidence of CLABSIs in limited-resource countries has not been explored analytically. Likewise, the appropriate interventions to prevent, control, and reduce CLABSIs have yet to be analyzed thoroughly. This review demonstrates that the CLABSI rate ranged from 1.6 to 44.6 cases per 1000 central line days in adult and pediatric intensive care units (ICUs) and from 2.6 to 60.0 cases per 1000 central line days in neonatal ICUs and is associated with significant extra mortality, with an odds ratio ranging from 2.8 to 9.5. The results of 6 sequential prospective interventional studies showed that hand hygiene and educational programs were related to a significant reduction in CLABSI rates. CLABSI rates in limited-resource countries are higher than US National Healthcare Safety Network benchmark rates and have a significant impact on mortality. Studies showing successful interventions for a reduction in CLABSIs are few. Subsequently, it can be inferred that additional epidemiological studies need to be conducted to achieve an appreciation of the effects of CLABSIs and to develop more-definitive approaches for CLABSI prevention in the form of practical, low-cost, low-technology measures that are feasible to implement in limited-resource countries.