Acute lymphocytic leukemia (ALL) is a hematologic malignancy induced by the uncontrolled proliferation of lymphoid progenitor cells. It is the most frequent malignancy in the pediatric population and it requires prompt treatment. Thus, comprehending its pathophysiological mechanisms is of paramount importance. Matrix metalloproteinases (MMPs) are a group of enzymes that degrade components of the extracellular matrix and have been shown to promote the progression of leukemia. Moreover, polymorphisms of genes encoding these enzymes are known to contribute to higher susceptibility to various cancers and poorer prognosis. This narrative mini-review explores the role of MMPs in the pathophysiology of ALL, the association between the polymorphism of their respective genes and the risk of ALL carcinogenesis and metastasis, as well as the potential role of the enzymes as clinical markers and therapeutic targets in ALL.