Cachexia is a multifactorial syndrome that includes muscle wasting and inflammation, and that is associated with chronic underlying diseases, such as cancer, chronic heart failure and chronic kidney disease. Since gut microbes influence host immunity and metabolism, we hypothesized a few years ago that the gut microbiota could be a potential therapeutic target to tackle cancer-related cachexia. In this review, we present evidence from animal and human studies suggesting that the gut microbiota and its crosstalk with the intestine might constitute unexpected targets in the therapeutic management of cancer and related cachexia. Finally, we discuss future research directions and hypotheses to progress in this new promising field, i.e. the role of the gut microbiota in cancer cachexia.