This review examines the neurobiological effects of pediatric cancer-related posttraumatic stress symptoms (PTSS). We first consider studies on prevalence and predictors of childhood cancer-related PTSS and compare these studies to those in typically developing (i.e., noncancer) populations. Then, we briefly introduce the brain regions implicated in PTSS and review neuroimaging studies examining the neural correlates of PTSS in noncancer populations. Next, we present a framework and recommendations for future research. In particular, concurrent evaluation of PTSS and neuroimaging, as well as sociodemographic, medical, family factors, and other life events, are needed to uncover mechanisms leading to cancer-related PTSS. We review findings from neuroimaging studies on childhood cancer and one recent study on cancer-related PTSS as a starting point in this line of research.