Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Although most of the children are cured by standard therapies, there is still need for new therapeutic biomarkers that can help children who don’t respond to current therapy. The resistance development and long-term side effects of current broad cytotoxic therapy of ALL has also warranted more novel targeted therapeutics. Childhood ALL is a heterogeneous disease where gene expression profiling has identified numerous genomic aberrations which has aided in classification of the disease into several subtypes. However, this classification is merely of prognostic value and and has not resulted in discovery of oncoproteins that can currently be targeted using therapeutics in the clinic. It’s apparent that genomic profiling does not always translate into oncogenic drivers that can be used as therapeutic targets. Lately many studies have highlighted the need and potential of mass spectrometry based proteomic approaches for characterization of ALL. Nevertheless, there is still a lack of comprehensive and in-depth studies of the proteome in childhood ALL. Therefore, global proteomics and proteogenomics provides an excellent additional layer to understand how and which genetic aberrations influence the molecular cancer phenotype on a systems level for therapeutic biomarker discovery.