Leishmaniasis is a protozoan parasitic infection that can manifest as visceral or cutaneous disease. Immunosuppression, mainly through TNF-α) inhibition, is a risk factor for complicated leishmaniasis that is becoming increasingly known. Here, we present a case of cutaneous leishmaniasis (CL) in a patient who suffers from advanced Takayasu-Arteritis, requiring TNF-α inhibition with infliximab. The primary CL lesions in this 47-year-old, female patient were caused by Leishmaniapanamensis and occurred after a touristic trip to Panama on her right foot. The lesions first resolved under treatment with liposomal amphotericin B. However, ten months later, the patient returned with relapsing lesions requiring further treatment. We discuss the challenges and risks of leishmaniasis in patients with TNF-α inhibition and the rare phenomenon of relapsing CL and the management hereof. We review published cases of CL associated with TNF-α inhibition. A growing body of evidence now suggests that especially CL (and visceral leishmaniasis (VL)) can be associated with TNF-α inhibition. The host response to leishmaniasis is of the Th1-type and TNF-α and interferon-gamma expression are crucial for disease control. Inversely, TNF-α inhibition can lead to complicated and relapsing progression of leishmanial infection. Therefore, we propose that CL and VL should be considered in at-risk patients receiving immunosuppressants.