Abstract: Immune checkpoint inhibitors (ICIs) have substantially improved the long-term survival in a subset of patients with multiple tumor types. However, some patients may develop a hyperprogressive disease (HPD) when they first start taking ICIs. The presence of HPD is always associated with deleterious outcomes and a poor quality of life. The evaluation of HPD is mostly based on a tumor growth ratio that is defined as the log-scale calibrated change in the sum of the longest diameters of the target lesions per month according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Several hypotheses have been proposed to elucidate the underlying mechanisms of HPD. Aberrant alterations in driver gene expressions, cancer microenvironments, or T-cell phenotypes may be the cause of HPD. Distinguishing between HPD and a naturally progressive disease remains a major enigma. Some clinicopathological characteristics and molecular biomarkers may have predictive values for HPD. In this review, we aimed to summarize the definition, evaluation, prevalence, potential predictors, and underlying mechanisms of HPD.