Cutaneous T-cell lymphomas (CTCLs) are a rare group of mature T-cell lymphomas presenting primarily in the skin. The most common subtypes of CTCL are mycosis fungoides and its leukaemic variant Sézary's syndrome. Patients with early-stage disease frequently have an indolent clinical course; however, those with advanced stages have a shortened survival. For the treating physician, the question of how to choose a particular therapy in the management of CTCL is important. These diseases span the disciplines of dermatology, medical oncology and radiation oncology. Other than an allogeneic stem cell transplant, there are no curative therapies for this disease. Hence, many treatment modalities need to be offered to the patient over the course of their life. An accepted treatment approach has been to delay traditional chemotherapy, which can cause excessive toxicity without durable benefit. More conservative treatment strategies in the initial management of CTCL have led to the development of newer biological and targeted therapies. These therapies include biological immune enhancers such as interferon alpha and extracorporeal photopheresis that exert their effect by stimulating an immune response to the tumour cells. Retinoids such as bexarotene have been shown to be effective and well tolerated with predictable adverse effects. The fusion toxin denileukin diftitox targets the interleukin-2 receptor expressed on malignant T cells. Histone deacetylase inhibitors such as vorinostat and romidepsin (depsipeptide) may reverse the epigenetic states associated with cancer. Forodesine is a novel inhibitor of purine nucleoside phosphorylase and leads to apoptosis of malignant T cells. Pralatrexate is a novel targeted antifolate that targets the reduced folate carrier in cancer cells. Lastly, systemic chemotherapy including transplantation is used when rapid disease control is needed or if all other biological therapies have failed. As response rates to most of the biological agents used to treat CTCL are 25-30%, it is also reasonable to consider clinical trials with novel agents if one or two front-line therapies have failed, especially before considering chemotherapy. CTCL is largely an incurable disease with significant morbidity and more active agents are needed.