The chapter discusses the significant advancements in cancer therapy over the past decade, particularly the introduction and widespread use of immune-checkpoint inhibitors (ICIs). These inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, and durvalumab, have revolutionized cancer treatment by targeting T cells and blocking immune checkpoints like CTLA-4, PD1, and PDL1. This has led to remarkable clinical efficacy in treating various cancers, including metastatic melanoma, and has transformed how treatment efficacy and toxicity are evaluated. Before the era of ICIs, solid tumor immunotherapy was in a poor state, relying on ineffective and toxic immunocytokines and cancer vaccines. However, the success of ICIs has reversed this situation, leading to a more holistic view of cancer management. New preclinical models using immune-competent animals have been developed, and clinical trials now incorporate immune parameters such as tumor-infiltrating T cells and tumor mutational burden (TMB). ICIs have also introduced new evaluation criteria, such as the iRECIST system, and modified clinical trial endpoints to better capture the delayed effects of these treatments. Adverse events associated with ICIs are different from those of previous therapies, often involving immune-mediated inflammation and severe reactions. Despite these challenges, ICIs have shown promise in achieving long-term remission in some patients, particularly in melanoma, where complete responses and durable remission after treatment discontinuation have been documented. However, the success of ICIs is limited to a minority of patients, and their effectiveness varies across different cancer types. The chapter concludes by highlighting the need for further research to identify biomarkers and optimize treatment regimens, while acknowledging the high expectations and potential disappointments that come with the success of this new therapy.The chapter discusses the significant advancements in cancer therapy over the past decade, particularly the introduction and widespread use of immune-checkpoint inhibitors (ICIs). These inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, and durvalumab, have revolutionized cancer treatment by targeting T cells and blocking immune checkpoints like CTLA-4, PD1, and PDL1. This has led to remarkable clinical efficacy in treating various cancers, including metastatic melanoma, and has transformed how treatment efficacy and toxicity are evaluated. Before the era of ICIs, solid tumor immunotherapy was in a poor state, relying on ineffective and toxic immunocytokines and cancer vaccines. However, the success of ICIs has reversed this situation, leading to a more holistic view of cancer management. New preclinical models using immune-competent animals have been developed, and clinical trials now incorporate immune parameters such as tumor-infiltrating T cells and tumor mutational burden (TMB). ICIs have also introduced new evaluation criteria, such as the iRECIST system, and modified clinical trial endpoints to better capture the delayed effects of these treatments. Adverse events associated with ICIs are different from those of previous therapies, often involving immune-mediated inflammation and severe reactions. Despite these challenges, ICIs have shown promise in achieving long-term remission in some patients, particularly in melanoma, where complete responses and durable remission after treatment discontinuation have been documented. However, the success of ICIs is limited to a minority of patients, and their effectiveness varies across different cancer types. The chapter concludes by highlighting the need for further research to identify biomarkers and optimize treatment regimens, while acknowledging the high expectations and potential disappointments that come with the success of this new therapy.