Drug-induced thrombocytopenia (DITP) remains a significant adverse event characterized by decreased platelet counts following medication exposure. This review examines both immune and non-immune mechanisms of DITP pathophysiology, diagnostic challenges, and current management strategies. While laboratory testing sensitivity remains limited, early recognition and prompt discontinuation of suspected medications form the cornerstone of treatment, with platelet transfusions and immunoglobulin therapy reserved for severe cases. Novel diagnostic approaches, including megakaryocyte-based assays, may improve future risk assessment and patient outcomes in DITP.