PURPOSE OF REVIEW: This review aims to outline the current understanding of the molecular drivers and treatment paradigms of gastrointestinal stromal tumors, with a focus on recent developments in treatment in the advanced disease setting. RECENT FINDINGS: There have been recent advancements in our understanding of the molecular biology of gastrointestinal stromal tumors, including the identification of new genetic drivers and complex resistance mechanisms. We review the most recent findings in these areas, focusing on how new research insights are reshaping treatment strategies. Recent advancements in our understanding of the biology and treatment of GIST are paving the way for more personalized and effective therapeutic options. As knowledge of rare molecular subtypes, resistance mechanisms, and novel genomic techniques grows, new approaches are emerging in an effort to improve patient outcomes.