Acute leukemia represents 31% of all cancers diagnosed in children and 80% of it is of Lymphoblastic type. Multiple genetic lesions in the hematopoietic progenitor cells prior to or during differentiation to B and T cell lead to development of leukemia. There are several subtypes of Acute Leukemia based on chromosome number changes, the presence of certain translocations and gene mutations, each of which has different clinical, biological and prognostic features. High throughput genomic technologies like array-based comparative genomic hybridization (array-CGH) and single nucleotide polymorphism microarrays (SNP arrays), have given us insight through a very detailed look at the genetic changes of leukemia, specifically, ALL. Here, we discuss various genetic mutations identified in Acute Lymphoblastic Leukemia. We also explore various genetic targets and currently available as well as upcoming targeted therapies for ALL.