Bloodstream infections (BSIs) are a frequent and life threatening condition in hospital settings. The case fatality rate associated with BSI reaches 35-50% when associated with admission to intensive care unit (ICU). The extensive use of intravascular catheters, however, is recognized as the most important factor contributing to the occurrence of BSI. Catheter-related BSIs (CR-BSIs) are the most common types of BSI in ICU. Bacteraemias that occur in the ICU are classified as Community Onset BSI and Hospital Acquired (HA) BSI. They are also distinguished in primary and secondary. Community-onset BSIs are those that occur in outpatients or are first identified 48 h after admission to hospital/ICU, and they may be sub classified further as health care associated (HCA), when they occur in patients with significant prior health care exposure, or community associated, in other cases. Hospital Acquired (HA) and / or ICU-acquired BSIs are defined as those occurring more than 48 hours after the patient's admission into the hospital or ICU or within 48 hours of leaving the hospital or the ICU. Community acquired BSIs usually due to susceptible bacteria should be clearly differentiated from HCA and HA BSIs frequently due to resistant hospital strains. A bedridden status, presence of indwelling devices, recent hospitalization or contact with health care facilities and recent antibiotic therapy may represent the most important risk factors for the development of emerging multi drug resistant (MDR) GN infections. The basic components of the treatment of a bacteraemia in the ICU are determining the type of bacteraemia in order to target potential pathogens, the initiation of empirical antimicrobial therapy based on the guidelines, and the source control if it is a secondary bacteremia. These goals become difficult to achieve in case of BSI due to multi-drug resistant pathogens with high MICs to antimicrobials. The main mechanisms which have put in danger the marvelous antibiotic weapon are the production of ESBL (several different subtypes), the production of carbapenemases and metallo-betalactamases, with consequent spread of multi or pan-resistant organism and the emerging growing resistance in colistin. The targeted treatment should be applied immediately after receiving the susceptibility test from the cultures. Targeted treatment essentially consists in redefining antibiotic treatment, in de-escalation in order to decrease the antibiotic selection pressure, and in determining the duration of treatment. Source control is recognized as an important part of the therapy of BSIs and has been recently shown to be independently related with outcome. Depending on the source of the infection (pneumonia, CRBSIs, urinary tract infections, intra-abdominal infections), the therapeutic strategy should be based on international guidelines in combination with local microbiology and local antibiotic resistance data.