David C. Fisher, MD; Lauren C. Pinter-Brown, MD; Barbara Pro, MD; and Sima Rozati, MD, PhD, discuss how to optimize cutaneous T-cell lymphoma treatment through multidisciplinary care; compartment-specific therapy selection; management of treatment-related complications, such as mogamulizumab-associated rash; and strategic use of combination therapies while addressing critical unmet needs including biomarker development and improved quality of life measures.