Fortilin is a highly conserved 172-amino-acid polypeptide found in the cytosol, nucleus, mitochondria, extracellular space, and circulating blood. It is a multifunctional protein that protects cells against apoptosis, promotes cell growth and cell cycle progression, binds calcium (Ca2 +) and has antipathogen activities. Its role in the pathogenesis of human and animal diseases is also diverse. Fortilin facilitates the development of atherosclerosis, contributes to both systemic and pulmonary arterial hypertension, participates in the development of cancers, and worsens diabetic nephropathy. It is important for the adaptive expansion of pancreatic β-cells in response to obesity and increased insulin requirement, for the regeneration of liver after hepatectomy, and for protection of the liver against alcohol- and ER stress-induced injury. Fortilin is a viable surrogate marker for in vivo apoptosis, and it plays a key role in embryo and organ development in vertebrates. In fish and shrimp, fortilin participates in host defense against bacterial and viral pathogens. Further translational research could prove fortilin to be a viable molecular target for treatment of various human diseases including and not limited to atherosclerosis, hypertension, certain tumors, diabetes mellitus, diabetic nephropathy, hepatic injury, and aberrant immunity and host defense.