The field of histamine research has progressed far from a century ago when the first biological functions of histamine were identified. It is now known that histamine function is mediated by four histamine receptors, which belong to the G-protein-coupled receptor family. While antihistamines that target the first two receptors have enjoyed clinical and commercial success, efforts to find new antihistamines against the histamine H3 and H4 receptors are still in the early stages. Here we will review the therapeutic potential of targeting these new histamine receptors.