BACKGROUND: Treatment options for drug-resistant tuberculosis (DR-TB) are limited. Linezolid has been successfully used to treat DR-TB in adults, but there are few case reports of its use in children for TB. The reported rate of adverse events in adults is high. METHODS: We conducted a retrospective review of children with DR-TB treated with linezolid-containing regimens from February 2007 to March 2012 at two South African hospitals. RESULTS: Seven children (three human immunodeficiency virus [HIV] infected) received a linezolid-containing regimen. All had culture-confirmed DR-TB; five had previously failed second-line anti-tuberculosis treatment. Four children were cured and three were still receiving anti-tuberculosis treatment, but had culture converted. None of the non-HIV-infected children experienced adverse events while receiving linezolid. Three HIV-infected children had adverse events, one of which was life-threatening; linezolid was permanently discontinued in this case. Adverse events included lactic acidosis (n = 1), pancreatitis (n = 2), peripheral neuropathy (n = 1) and asymptomatic bone marrow hypoplasia (n = 1). CONCLUSION: Linezolid-containing regimens can be effective in treating children with DR-TB even after failing second-line treatment. Adverse events should be monitored, especially in combination with medications that have similar adverse effects. Linezolid remains costly, and a reduced dosage and duration may result in fewer adverse events and lower cost.