Immune checkpoint inhibitors (ICIs) have robust therapeutic efficacy, offering sustained clinical benefit in various malignancies. However, the optimal duration of treatment remains under investigation. This review summarizes recent trends in long-term ICI therapy, with particular focus on hepatocellular carcinoma (HCC). The conventional 2-year treatment limitation, initially based on data from non-small cell lung cancer trials (e.g., KEYNOTE-010, Check-Mate-017), has been adopted broadly across tumor types. Follow-up data suggest that many patients maintain remission even after discontinuation of treatment, prompting reevaluation of prolonged therapy necessity. In HCC, atezolizumab plus bevacizumab has become the firstline standard treatment, but questions persist regarding continuation beyond two years and post-progression management. Emerging data indicate that salvage therapies—including tyrosine kinase inhibitors like sorafenib or lenvatinib—remain viable options after ICI failure. Furthermore, recent studies from European cohorts and Asian populations have provided insights into long-term survival, treatment sequencing. This review aims to provide a clinical and practical overview of these evolving paradigms to guide personalized, evidence-based decisions in immune-oncology.