Pediatric oncology patients are at risk for developing a headache after they undergo a lumbar puncture for diagnostic or therapeutic purposes. These headaches are likely due to leakage of cerebrospinal fluid at the puncture site. While usually mild and self-limited, some headaches may be persistent and severe, adding to the distress of these young patients. In the past 10 years, refinements in lumbar needle size and shape as well as procedural techniques have reduced the tissue trauma that predisposes patients to headache. A number of interventions, such as bed rest, hydration, caffeine administration, and epidural blood patching, have been suggested to prevent and relieve the headaches that follow lumbar punctures. This article outlines the pathophysiology and incidence of headaches related to lumbar punctures in the pediatric oncology setting and reviews the evidence from research trials to suggest which interventions clinicians should adopt into their practice to minimize this complication of lumbar punctures.