Significant progress in our understanding of cancer cachexia has occurred in recent years. Despite these advances, no pharmacologic agent has achieved US Food and Drug Administration approval for this common and highly morbid syndrome. Fortunately, improved understanding of the molecular basis of cancer cachexia has led to novel targeted approaches that are in varying stages of drug development. This article reviews two major thematic areas that are driving these pharmacologic strategies, including those targeting signal mediators at the level of the CNS and skeletal muscle. Additionally, pharmacologic strategies are being tested in combination with targeted nutrients, nutrition therapy, and exercise to treat cancer cachexia. To this end, we highlight recently published and ongoing trials evaluating cancer cachexia therapies in these specific areas.