Bloodstream infections (BSI) constitute a significant public health problem and represent an important cause of morbidity and mortality in hospitalized patients, with an approximate incidence of one episode per hundred hospital admissions. Studies on BSI in HIV+ patients have identified central venous catheters (CVC) as a risk factor, with an attributable mortality rate of 10-20%. The long-term CVC-related infection risk appeared to be 5 to 10-fold higher with respect to the infection rates among HIV- patients. CVC associated infection rate ranges from 1.3 to 12 infections per 1,000 catheter-days. Staphylococcus aureus is the most common etiologic agent causative of CVC-related BSI, likely the result of the high skin and nasal carriage of this organism among HIV+ patients, mostly intravenous drug users. Coagulase-negative staphylococci are also frequently identified as cause of CVC-related BSI, likely the result of breaches in infection control measures and in antiseptic technique during CVC management. Treating bacteremia without catheter removal would be optimal, but the reported efficacy of systemic antibiotic therapy alone is only 25-32%. Conversely, recent studies have shown that, using an antibiotic-lock procedure, up to 90% of HIV-infected and uninfected patients achieved complete eradication of catheter-related BSIs without catheter removal. Clinical trials using new materials such as covalently linked heparin on the CVC surface, electrically charged CVC, novel topical agents that interfere with bacterial colonization, antiadhesin molecules and agents that block the gene expression involved in the biofilm formation, are all needed to reduce the high catheter-related infection risk among HIV+ patients.