About 250,000 bloodstream infections are diagnosed each year, and most are related to the presence of intravascular devices [
1]. Central line-associated bloodstream infections (CLABSI) are defined as a laboratory-confirmed bloodstream infection that recognize a central line as the focus of infection, typically occurring > 48 h after central line placement [
2]. It has been estimated that the CLABSI rate in the United States (U.S.) intensive care units (ICU) is 0.8 per 1000 central line days [
2]. The ICU surveillance data on 703 intensive care units in 50 countries, furnished by the International Nosocomial Infection Control Consortium (INICC) between January 2010 and December 2015, reported a CLABSIs rate of 4.1 per 1000 central line days [
3]. The higher rate of CLABSIs in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific, if compared to the incidence in the United States, seems to be due to insufficient resources and experience in infection control of the developing countries [
4]. It has to be noticed that compared to other healthcare-associated infections (ventilator-associated pneumonia, surgical site infections, Clostridium difficile infection, and catheter-associated urinary tract infections), CLABSIs are the costliest to manage, accounting for about
$46,000 per case in the United States. 2. CLABSIs are also among the most preventable health care infections. Institution of proper catheter care measures reduces CLABSI rate by 65–70% [
5]. Proper catheter care includes following aseptic techniques during insertion, identifying the best insertion site with a preference for subclavian vein insertion, surveillance measures, and management strategies. These prophylactic measures, described above, should have to lead to a relevant decrement of CLABSIs incidence. However, these complications are still not completely eliminated [
6,
7,
8]. Antimicrobial lock therapy (ALT) has been investigated in the prevention and treatment of central venous catheters-related infections. ALT consists, first, in the manual injection (“flush”) of a solution, generally normal saline, with the purpose of cleaning the inner lumen of the catheter, removing remnants of infused substances and maintaining its patency and, second in the filling of the catheter (“lock”) with a limited volume of the chosen lock solution in the intervals of time when the catheter is not in use, with the purpose of preventing lumen occlusion and/or bacterial colonization. G.A. Goossens in 2015, has clearly defined modalities of flushing and locking to take into account in our daily clinical practice [
9]. Catheter lock technique would have been the more appropriate term for this technique as it would include both antibiotic and non-antibiotic lock solutions. In the current terminology ALT refers to all the techniques regardless of the lock solution used. Over the past few years, several randomized trials have investigated ALT and yielded promising results [
10,
11]. However, there are concerns regarding the emergence of antibiotic-resistant organisms, noninfectious complications, and the inability of previous studies to prove the additive benefit of lock solutions in conjunction with catheter care bundles [
12,
13,
14]. All these factors delayed the inclusion of ALT into guidelines for the management of CLABSI until 2009 [
15]. These guidelines in the section for General Management of Catheter-Related Infection at the point number 30 suggest that ALT should be used for catheter salvage (B-II); however, if antibiotic lock therapy cannot be used in this situation, systemic antibiotics should be administered through the colonized catheter (C-III) [
15]. Hospitals have different institutional policies regarding CLABSI. According to the ALT Guideline at Stanford Hospital, this technique is highly recommended [
16]. The Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of CLABSI recommend ALT as adjunctive therapy specifically for catheter salvage in cases where the catheter is not removed [
15]. Furthermore, because of the efficacy of the ALT in pediatric patients, there are several pediatric hospitals that are developing and implementing ALT guidelines [
17]. The ESMO guidelines (2015) [
18] and the recent literature [
19], provide for the use of ALT in prevention for long-term infections associated with central venous catheters (CLABSI) in cancer patients. Even if several evidences support the use of ALT in seriously ill patients such as patients in need of palliative care, the effectiveness in patients in need of hemodialysis is still unclear [
20]. Despite the elaboration of all these clinical practice protocols or guidelines, the most appropriate lock solution for central venous access devices is still to be defined [
19]. Conceptually the ALT should be performed with a solution that a) has a low toxicity, b) cost-effective, c) has no risk of development of antibiotic microbial-resistance, d) has broad spectrum of activity, e) has no interaction with anticoagulant with a f) stability of antimicrobial activity over a prolonged period ( 24–48 h). There are several recent studies that tried to define the best lock solution to be used. These studies are different from each other according to their methodology and setting ranging from the network meta-analysis by Dang et al. published in 2019, to experimental models such as that proposed by Basas J. and colleagues. According to Dang et al. minocycline-ethylenediaminetetraacetic acid (EDTA) is effective in the prevention of CRBSI and exit-site infection [
21], while the study by Basas J. et al. on rabbit model showed that liposomal amphotericin B (LAmB) ALT or anidulafungin ALT can be used to treat CLABSIs infections by Candida glabrata and Candida albicans [
22]. Because of the wide range of available evidence on CLABSIs management, this scoping review unlike the previous systematic reviews [
23] does not aim to give recommendations on the use of ALT but aims to furnish a map and a synthesis on this topic, offering a base for the development of new clinical practice indications and health policies. This scoping review aims to summarize the main indications for ALT and list the lock therapy solutions described in literature (not only antibiotic solutions). The systematic and validated review approach avoids the risk of generating conclusions based on studies of debatable quality.