Despite remarkable progress in the elucidation of energy balance and regulation, the development of new antiobesity drugs is still at the stage of infancy. This review describes the MCH and MCH receptor system with regard to its involvement in energy homeostasis and summarizes the pharmacological profiles of selected small molecule MCH-R1 antagonists that are relevant for their development as antiobesity drugs. Although their clinical value still has to be demonstrated, and challenges with regard to unwanted side effects remain to be resolved, MCH-R1 antagonists may provide an effective pharmacotherapy for the treatment of obesity in the near future.