The prevalence of obesity raises public health concern about the consequences of this alarming epidemic. Musculoskeletal disorders of the knee joint such as osteoarthritis (OA) and general knee pain, the leading causes for disability in the elderly, are increased in those who are overweight. Understanding of the etiology of OA and the biomechanical contribution of obesity may assist researchers and clinicians to identify those subjects who may be at risk. Additional biomechanical risk factors such as adduction moment and malalignment have been identified, but confounding systemic factors and differences in methods have resulted in disagreement of whether risk of onset is increased. It is not known whether adaptations, such as increases in bone size or bone strength, can be sufficient to compensate for the larger forces in those who are overweight. The goals of this dissertation were to use a three-dimensional finite element (FE) model as a tool to investigate the effects of obesity, adduction moment, geometry and bone density, by predicting the trabecular bone stresses and strains immediately below the subchondral bone. A magnetic resonance imaging method to non-invasively predict in vivo trabecular bone material properties was established and used as input into the finite element models. Comparing FE models of one normal weight subject to one who was obese, we demonstrated that an individual might not have increased trabecular bone stress or strains simply because of their increased weight, but that adduction moment must also be considered. Using a design of experiments approach, body weight and adduction moment were determined to be the largest contributors to variations in predicted trabecular bone stress, while mean trabecular bone material properties were critical when predicting trabecular bone strain. Trabecular bone and articular cartilage stresses predicted from our FE model were significantly correlated to odds ratios for onset of OA determined from large clinical studies and established the relevance of predicted increases of trabecular bone stress and strain as increased risk of OA onset. This study is the first to quantify increasing proximal tibial trabecular bone stress and strain due to obesity and relate these mechanical consequences to risks for OA onset. This data adds to the current understanding of the biomechanical risk factors related to knee pain or OA onset and may assist the clinician in design of safe and effective exercise programs.