Atrial fibrillation is the most prevalent sustained cardiac arrhythmia, characterized by limited therapeutic options because of incompletely understood mechanisms of its development. The key underlying pathogenetic mechanisms involve atrial myocardial inflammation and fibrosis in response to pressure or volume overload, myocardial infarction, as well as metabolic alterations. Recent studies have highlighted the crucial role of osteopontin in diverse cardiovascular diseases, including atrial fibrillation. Osteopontin is a multifunctional extracellular matrix protein that has recently emerged as a potential mediator of atrial remodeling and arrhythmogenesis. Human studies have revealed that circulating osteopontin levels can serve as a valuable biomarker for atrial fibrillation and its progression. Furthermore, in vitro studies have demonstrated that osteopontin modulates several key cellular processes involved in atrial inflammation and fibrosis, including fibroblast activation, extracellular matrix remodeling, and proinflammatory cytokine production. This review critically examines the available evidence on the role of osteopontin in atrial remodeling and arrhythmia starting from the molecular mechanisms by which osteopontin contributes to structural and electrical remodeling of the atria, to its potential as a biomarker for atrial fibrillation.