The review discusses the use of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway inhibitors, particularly tofacitinib, in managing immune checkpoint inhibitor (ICI)-induced colitis. While ICI therapy has shown significant efficacy in treating various cancers, it can also cause severe gastrointestinal toxicity, including ICI colitis. Current guidelines recommend corticosteroids or biologic drugs like infliximab or vedolizumab for treating ICI colitis, but JAK-STAT inhibitors are not widely recommended. The review highlights that tofacitinib has been reported to induce clinical remission of ICI colitis without affecting the underlying neoplasm's oncologic progression. Several case reports and series studies have demonstrated the effectiveness of tofacitinib in treating ICI colitis, especially in patients who have failed conventional and advanced treatments. However, the precise mechanisms by which JAK-STAT inhibitors, particularly tofacitinib, exert their effects on ICI colitis remain unclear. Further research is needed to understand the role of JAK-STAT inhibitors in managing ICI colitis, including their potential impact on memory CD8+ T lymphocytes. The ongoing TRICK study aims to evaluate the efficacy of tofacitinib in treating refractory ICI colitis, providing valuable insights into this therapeutic approach.The review discusses the use of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway inhibitors, particularly tofacitinib, in managing immune checkpoint inhibitor (ICI)-induced colitis. While ICI therapy has shown significant efficacy in treating various cancers, it can also cause severe gastrointestinal toxicity, including ICI colitis. Current guidelines recommend corticosteroids or biologic drugs like infliximab or vedolizumab for treating ICI colitis, but JAK-STAT inhibitors are not widely recommended. The review highlights that tofacitinib has been reported to induce clinical remission of ICI colitis without affecting the underlying neoplasm's oncologic progression. Several case reports and series studies have demonstrated the effectiveness of tofacitinib in treating ICI colitis, especially in patients who have failed conventional and advanced treatments. However, the precise mechanisms by which JAK-STAT inhibitors, particularly tofacitinib, exert their effects on ICI colitis remain unclear. Further research is needed to understand the role of JAK-STAT inhibitors in managing ICI colitis, including their potential impact on memory CD8+ T lymphocytes. The ongoing TRICK study aims to evaluate the efficacy of tofacitinib in treating refractory ICI colitis, providing valuable insights into this therapeutic approach.