Obesity is linked to increased cancer risk. Pathological expansion of adipose tissue impacts adipocyte function and secretion of hormonal factors regulating tissue homeostasis and metabolism. Adiponectin is an adipocyte-secreted, circulating hormone with pleiotropic functions in lipid and glucose metabolism, and beneficial roles in cardiovascular functions and inflammation. In obesity, decreased Adiponectin plasma levels correlate with tumor development and progression. The association of Adiponectin with potential tumor-limiting functions has raised significant interest in exploring this adipokine as a target for cancer-diagnostic and therapeutic applications. Recent studies, however, also implicate Adiponectin in supporting malignancy. This review highlights the evidence that links Adiponectin signaling to either cancer-protective or cancer-supporting functions. In this context, we discuss Adiponectin interactions with its receptors and associated signaling pathways. Despite significant advances in understanding Adiponectin functions and signaling mechanisms, its role in cancer remains multifaceted and subject to controversy.