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Despite their abundance throughout the body, adipocytes are often ignored for their contributions within the tumor microenvironment (TME). However, their role in fueling cancer is becoming increasingly apparent as interest in the TME has seen remarkable advances in recent years. A seminal study by Dirat and colleagues highlighted the essential impact of the peritumoral adipose tissue in breast cancer progression and was among the first to demonstrate that tumor cells can reprogram adipocytes within their immediate niche to adopt unique characteristics. These "cancer-associated adipocytes" (CAA) were found to exchange cytokines and lipids with tumor cells, leading to their metabolic rewiring and acquisition of proinflammatory and invasive phenotypes. These important discoveries have represented a breakthrough in understanding the bidirectional metabolic dialog between adipocytes and tumor cells, and have contributed renewed perspectives on the functional contributions of adipocytes within the TME. Moreover, the effects of CAA may be further amplified in the setting of obesity as lipids dramatically accumulate, providing insights into the link between breast cancer and its more advanced clinical state in obese conditions. Thus, the different molecular actors involved in the dialog between tumor cells and CAA represent promising therapeutic targets that may have particular relevance in improving prognosis in obese patients with cancer. See related article by Dirat and colleagues, Cancer Res 2011;71:2455-65., (©2023 American Association for Cancer Research.)