Cell adhesion manifests as cell linkages to neighboring cells and/or the extracellular matrix (ECM). Migfilin is a widely expressed adhesion protein. It comprises three LIM domains in the C-terminal region and one proline-rich sequence in the N-terminal region. Through interplay with its various binding partners, such as Kindlin-2, Filamin, vasodilator-stimulated phosphoprotein (VASP) protein and the transcription factor CSX, Migfilin facilitates the dynamic association of connecting actomyosin fibers, orchestrating cell morphogenetic movement and cell adhesion, proliferation, migration, invasion, differentiation and signal transduction. In this review, to further elucidate the functional contributions of and pathogenesis induced by Migfilin, we focused on the structure of Migfilin and the targets which it directly binds with. We also summarized the role of Migfilin and its binding partners in the progression of different diseases and malignancies. As a possible candidate for coordinating various cellular processes and because of its association with both the pathogenesis and progression of certain tumors, Migfilin likely has utility as a therapeutic target against multiple diseases in the clinic.