In the strategic management of mycosis fungoides (MF)/Sézary syndrome (SS), an interdisciplinary framework is essential. The regimen typically encompasses dermatological-specific interventions, biologic response modulators, and, in advanced scenarios, systemic chemotherapeutic entities. This might integrate biologic response agents like bexarotene, histone deacetylase inhibitors such as romidepsin, and specialized monoclonal antibodies or conjugates, notably mogamulizumab and brentuximab vedotin. Decisions in therapeutic avenues are intricately individualized, considering determinants like patient age, functional health metrics, disease scope, evolutionary trajectory and previous therapeutic exposures. The high-frequency ultrasound seems to be a useful tool for monitoring infiltration of the skin. Moreover, ongoing studies are investigating novel therapeutic agents that may demonstrate efficacy in MF/SS.