Higher levels of body fat are associated with increased risk for development of numerous adverse health conditions. Phytochemicals are potential agents to inhibit differentiation of preadipocytes, stimulate lipolysis, and induce apoptosis of existing adipocytes, thereby reducing adipose tissue mass. Resveratrol decreased adipogenesis and viability in maturing preadipocytes; these effects were mediated not only through down-regulating adipocyte specific transcription factors and enzymes but also by genes that modulate mitochondrial function. Additionally, resveratrol increased lipolysis and reduced lipogenesis in mature adipocytes. In addition, combining resveratrol with other natural products produced synergistic activities from actions on multiple molecular targets in the adipocyte life cycle. Treatment of mice with resveratrol alone was shown to improve resistance to weight gain caused by a high-fat diet. Moreover, dietary supplementation of aged ovariectomized rats with a combination of resveratrol and vitamin D, quercetin, and genistein not only decreased weight gain but also inhibited bone loss. Combining several phytochemicals, including resveratrol, or using them as templates for synthesizing new drugs, provides a large potential for using phytochemicals to target adipocyte adipogenesis, apoptosis, and lipolysis. © 2011 New York Academy of Sciences.