The targeted agents have considerably modified the therapeutic approach of cancer over the last few years. The use of these new agents has been associated with the occurrence of new side-effects among which cutaneous side-effects are the most prominent. Although they rarely compromise the vital prognosis, these cutaneous side-effects must be taken into consideration in order to improve treatment compliance and to maintain an acceptable quality of life. Accurate identification of these cutaneous side-effects is therefore critical to improve the management of these patients. A better understanding of the mechanisms underlying cutaneous signs is also an important issue as it gives us the opportunity to increase our knowledge of the skin pathophysiology. Furthermore, the cutaneous manifestations could sometimes be associated to the antitumor response. The skin is an easily accessible interface, allowing addressing the complexity of the targeted therapies effect on tissues.