The following chapter details current understanding of interactions between insulin, or insulin resistance, obesity, and mood and affect as key mediators of this association. The functions of insulin in the periphery and central nervous system are reviewed, and insulin resistance is explained. Three different levels of affective states are defined: Pure affect, mood, and emotion, although it is noted that more research currently focuses on mood and mood disorders. Insulin crosses the blood-brain barrier using saturable transporters, whereupon it influences a range of functions ranging from memory to the regulation of mood and reward-seeking behaviors including eating. The review notes striking similarities between the neurological consequences of diabetes and depressive illness, including decreases in hippocampal formation volume. Hence, the development of insulin resistance would appear to disrupt these systems, contributing to the development of mood disorders such as major depressive disorder and the overconsumption of calorie-dense foods. The precise mechanisms for these processes remain unclear and are likely to be highly complex and multifaceted. Possible mechanisms for these relationships are outlined, including insulin resistance, HPA-axis dysfunction, autonomic nervous system imbalance, endothelial dysfunction, platelet overactivity, inflammation responses, and chronic psychosocial distress. Any or all of these systems offer plausible explanations, and there is no reason to suppose that there is only one correct option from those listed. In addition to studying the cellular and physiological levels of analysis, research must incorporate consideration of the subjective experiences generated by these systems. In particular, there may be explanatory value in examining the less stable short-term experiences of emotions, as well as more stable mood states.