Obesity is a serious problem in the United States and developing countries. Obesity leads not only to serious chronic health problems but is also associated with approximately 40% higher health care costs than normal weight individuals. Long standing theories of weight loss rested on the simplistic idea that one must expend more calories than one consumes. Although this is a mainstay of weight loss regimens, the underlying causes of obesity are more complex than previously considered. Research has noted nutritional deficiencies in subjects that are overweight, obese and morbidly obese. Is the cause of this contradictory deficiency due to low-cost, nutrient poor food or do findings suggest that there is an alteration in absorption, distribution, metabolism and/or excretion of these nutrients in overweight and obese individuals. Nutrient deficiencies in obese populations are very common with vitamin D deficiency being the most prevalent affecting approximately 57-94% of obese individuals. Interestingly, correction by protein-rich diet supplementation containing vitamins and minerals did not correct levels. In contrast, micronutrient levels remained low or became even lower. This discrepancy may be explained by gastrointestinal barrier dysfunction, intestinal microbiota or increased metabolic demand. There are also theories examining amino acid and neurotransmitter depletion that disrupts feedback mechanisms. There are several neurotransmitters that regulate weight, appetite and satiety. Findings suggest that a low level of neurotransmitters, amino acid precursors or receptors had a direct impact on a subject's weight. The review of research reveals that obesity is a complex problem with multiple contributing factors. Further understanding of the dietary deficiencies and the regulation of the metabolic pathway is fundamental towards effective treatment.