Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and 85% of cases are B-cell ALL (B-ALL). Although the prognosis is usually good, 10–15% of patients have relapsing or refractory disease, which can lead to poor outcomes. To aid in the development of better treatments for these patients, a new study investigated the role of netrin-1 in B-ALL, as this axon guidance protein has been linked to tumorigenesis in many cancers. In the study, serum netrin-1 levels were higher in children with B-ALL than in children without cancer, and when the children with B-ALL were grouped by risk stratification, the high- and intermediate-risk groups had higher netrin-1 levels than the low-risk group. In vitro, recombinant netrin-1 prevented apoptosis of B-ALL cells, thus supporting cancer cell survival by interacting with the receptor Unc5b to activate the FAK-MAPK pathway. However, netrin-1 did not affect B-ALL cell migration. Although the anti-apoptotic mechanism needs to be confirmed in vivo, the findings provide new insights into the pathology of B-ALL and suggest that netrin-1 could be a useful therapeutic target for this childhood cancer.