The combination of profound muscle wasting and severe weight loss that occurs in heart failure is a complex phenomenon that involves the interplay of numerous factors. In this article, we describe processes that contribute to cachexia, as part of the clinical sequelae of heart failure, and their potential underlying mechanisms. While multiple mechanisms of cardiac cachexia have been described, we propose a multifactorial etiology for this condition that includes, but is not limited to, nutritional and gastrointestinal alterations, immunological and neurohormonal activation, and anabolic and catabolic imbalance.