Pruritus is the main symptom of many dermatologic and systemic diseases. Atopic dermatitis, psoriasis, contact dermatitis, urticaria, lichen simplex chronicus, mycosis fungoides, scars, autoimmune diseases, kidney or liver diseases among others are all associated with itch that may require different approaches to management. Although antihistamines seem to be the first line of therapy, in reality their role is limited to urticaria and drug-induced reactions. In fact, the pathophysiologic mechanisms of each of the conditions covered in this review will differ. Recent years have seen the emergence of new drugs whose efficacy and safety profiles are very attractive for the management of pruritus in clinical practice. Clearly, we are at a critical moment in dermatology, in which we have the chance to be more ambitious in our goals when treating patients with pruritus.