In-transit melanoma represents a distinct disease pattern of heterogeneous superficial tumors. Many treatments have been developed specifically for this type of disease, including regional chemotherapy and a variety of directly injectable agents. Novel strategies include the intralesional delivery of oncolytic viruses and immunocytokines. The combination of intralesional or regional chemotherapy with systemic immune checkpoint inhibitors also is a promising approach. In the current review, we examine the general management of the workup of patients with in-transit disease, the range of available therapies, and recommendations for specific therapies for an individual patient.