The melanocortin system plays a pivotal role in the regulation of appetite and energy balance. It was recognized to play an important role in the development of cancer-related cachexia, a debilitating condition characterized by progressive body wasting associated with anorexia, increased resting energy expediture and loss of fat as well as lean body mass that cannot be simply prevented or treated by adequate nutritional support.The recent advances in understanding of mechanisms underlying cancer-related cachexia led to consequent recognition of the melanocortin system as an important potential therapeutic target. Several molecules have been made available for animal experiments, including those with oral bioavailability, that act at various checkpoints of the melanocortin system and that might confer singificant benefits for the patients suffering from cancer-related cachexia. The application of melanocortin 4 receptor antagonists/agouti-related peptide agonists has been however restricted to animal models and more pharmacological data will be necessary to progress to clinical trials on humans. Still, pharmacological targeting of the melanocortin system seem to represent an elegant and promising way of treatment of cancer-related cachexia.