The definition of unintentional weight loss (UWL) is heterogeneous and most commonly used as a UWL of >5% over the past 6 months. The differential diagnosis of UWL is very broad and encompasses non-medical causes, somatic illnesses, and psychiatric conditions. One of the feared diagnoses remains the presence of an underlying cancer. It is observed that UWL is more associated with certain types of cancer, in particular digestive. The primary workup for UWL should begin with a history and a detailed physical examination searching for associated symptoms or signs. The age, sex and smoking status are factors to be considered in particular. Management of UWL does not meet established recommendations and should be guided by relevant signs and symptoms. Future studies are necessary, in particular to clarify the place of imaging in the diagnostic process.