Those with severe mental illness represent one of the highest risk groups for cardiometabolic disease and premature death, losing up to 25 to 30 years of life. Many patients receive a variety of orexigenic psychotropic agents and - in some cases - weight gain and the cascade of effects from insulin resistance can be linked to these prescriptions. There are a variety of associations between the most well-known antipsychotics that are allied to cardiometabolic risk and both direct and indirect pharmacological models of action. Knowledge of some of these models can be helpful to clinicians in rationalising the use of psychotropic agents, especially antipsychotics such as olanzapine. In addition, heuristic models of action may also provide a framework for predicting the potential for other agents to cause weight and metabolic disturbances. This talk will focus on an overview of key models and present a hierarchy of risks related to the common classes of psychotropic agents.