Currently, cutaneous lymphomas represent a paradigm for the heterogeneity and the dynamic variability of neoplastic disorders resulting in the accumulation of clonal lymphocytes in the skin, and thus mirror the complexity of lymphocytic populations. Increasing knowledge and insight in pathobiology offer new opportunities for targeted interventions to selectively hit the tumor populations. mAbs, rexinoids, small kinase inhibitors, or molecules interfering with methylation or histone acetylation contribute to disease control. The rational and well-coordinated application of these tools, together with improved chemotherapeutic options, will hopefully further improve treatment success in the near future.