The relationship between obesity and prostate cancer is currently a hotly debated topic, but despite the number of publications devoted to the topic, the actual nature of the relationship remains uncertain. Obesity has been shown to have a direct relationship with the incidence of prostate cancer in a number of studies but an equal number of studies have shown no association. The relationship is further obscured with recent findings that obesity in younger obese men may actually be protective against prostate cancer. Confounding factors include the lack of correlation of body mass index (BMI) as a measure of central obesity and the lack of consistency in timing of BMI measurements, i.e. before or after diagnosis and in young or advanced adulthood. Evidence for increased BMI as a risk factor for prostate cancer is unclear, but less ambiguous is the mounting substantiation that obesity is associated with prognostically worse disease, poorer post-surgical outcomes and increased prostate cancer mortality, irregardless of margin status. From a biologic perspective, one can put forth a number of potential mechanisms by which obesity might promote prostate cancer and/or prostate cancer progression including; low levels of testosterone, increased levels of estrogen, co-existing diabetes or metabolic syndrome, increased circulating insulin-growth factor-one (IGF-1), increased levels of leptin, decreased levels of adiponectin and increased dietary saturated fats. Evidence for the association of these factors with prostate cancer are examined herein. The timing of serum measurements is crucial in elucidating whether these factors have causative influence on prostate cancer or rather are produced by the prostate cancer cells and are better understood as markers of disease. The interaction between obesity and prostate cancer is important to clarify because it will have impact on the prevention, prognostication and treatment of prostate cancer. Future study with careful attention to avoid the methodological pitfalls of the past need be accomplished to bear out the nature of the interaction of obesity and prostate cancer.