Development of obesity is characterized by hypertrophy and hyperplasia of adipocytes in white adipose tissue (WAT). This process relies on concomitant angiogenesis. Results from experimental inhibition or depletion of cells comprising the vasculature in animal models have contributed to the understanding of the mechanisms governing expansion of WAT. Disruption of neovascularization might be potentially useful for obesity prevention. In addition, approaches in which the mature WAT vasculature is disrupted have been sought with the aim of combating obesity after its onset. Other cell types in WAT, including adipose stromal cells, which support angiogenesis, could represent alternative targets for combinatorial WAT treatment. This review discusses recent advances in WAT vascular targeting and implications for the development of new anti-obesity therapeutics.