Acute lymphoblastic leukemia (ALL) is the most common cancer in children in the modern world. Recent efforts in characterizing the genetic contribution to this disease through uncovering gene mutations, deletions and structural variation by genome-scale methods have only accounted for a modest proportion of children with ALL. This suggests that either further genetic contributions to ALL have yet to be characterized or other factors, such as epigenetic aberrations are involved. A number of DNA methylation and miRNA profiling studies have investigated the role of both in childhood ALL. Here, we review these profiling efforts, summarize their major findings and speculate as to what the future may hold.