Bacterial infections are a major cause of morbidity and mortality in people who inject drugs (PWID). Patients with bacteraemia have a particularly high risk of complications and are usually treated with intravenous antibiotics. Intravenous treatment is challenging in certain PWID because of difficult venous access and a high rate of catheter-associated complications. Therefore, oral treatment alternatives must be considered. This review discusses the potential options for oral antimicrobial treatment of gram-positive and gram-negative bacteraemia in PWID and the evidence for them. Data on oral antibiotic treatment of bacteraemia in PWID is scarce. Whenever possible, a course of intravenous antibiotic treatment should precede the switch to an oral regimen. For Staphylococcus aureus bacteraemia, there is growing evidence that initial intravenous antibiotics can be switched to oral treatment (e.g., a fluoroquinolone and rifampin or linezolid) when the patient is clinically stable and source control has been achieved. However, regimen selection remains challenging due to pharmacokinetic/pharmacodynamic issues, potential toxicity and drug-drug interactions of oral antibiotics. For some streptococcal bacteraemia, oral amoxicillin is probably a reasonable option. The best existing evidence for oral antibiotic treatment is for gram-negative bacteraemia, which, if susceptible, can be treated successfully with oral fluoroquinolones. Oral antibiotic options for fluoroquinolone-resistant gram-negative bacteraemia are very limited, although in selected patients oral trimethoprim-sulfamethoxazole can be considered. In conclusion, treatment of bacteraemia in PWID remains very complex, and an interdisciplinary approach is essential in order to select the best therapy for this vulnerable group of patients.