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In the past 15 years, immunotherapy has become a major strategy for cancer therapy. Tumor-infiltrating lymphocyte (TIL) therapy has been under investigation for nearly four decades and received its first Food and Drug Administration approval in 2024, when lifileucel was approved for patients with previously treated metastatic melanoma. TIL therapy is a form of cell-based immunotherapy that uses autologous T cells isolated from the tumor microenvironment, which are expanded ex vivo and reinfused to mediate tumor regression after lymphodepleting chemotherapy and high-dose interleukin-2. Current data demonstrate durable responses in a subset of heavily pretreated patients with advanced melanoma, and early clinical studies suggest activity in other immunogenic solid tumors. In this review, the historical development of TIL therapy, its current clinical applications, emerging strategies to optimize product composition and the tumor microenvironment, and the critical role of surgeons in TIL procurement and delivery are summarized.