Tectonic uplift of the Tibetan Plateau (TP) is a major event in the recent geological history of the earth, which produced far-reaching impacts on the Asian and global climates and environments. Since the 1970s, with the development of theories in planetary fluid dynamics and the improvement of computational environment, numerical simulation based on general circulation models (GCMs) has become an increasingly effective tool in investigations of the physical mechanisms and evolutionary processes of paleoclimate associated with the TP uplift. In this paper, we provide a timely review on representative works in the past four decades on the paleoclimatic responses to the plateau uplift. Numerical simulations to study the paleoclimatic effects of the plateau uplift experienced three stages with increasing complexity: 1) plateau uplift as a whole in a single episode, as represented by the no-mountain/with-mountain experiments; 2) phased uplift in which the uplifting process was divided into multiple stages and within each the plateau rose by a certain proportion of its current height; and 3) sub-regional uplift, in which the focus was the effects of the uplift of a certain area within the TP, such as the northern Tibetan Plateau. These studies discovered the cause-effect relations between the plateau uplift and paleoclimate change, especially for the effects on the evolution of Asian monsoon system and aridiifcation of inland Asia. In this review, we also included examples of current on-going studies, such as the relative impacts of the Himalayas vs. those of the TP as the rain barrier and comparative studies on the paleoclimatic effects of the uplifts of the TP and African highland. Toward the end, we identiifed ifve areas as the focus of future research regarding the TP uplift: 1) the differences in the evolutionary processes of the South Asian and East Asian monsoons in response to the Himalayas–TP uplift at the regional and sub-regional scales; 2) climatic feedbacks; 3) long-distance effects (teleconnections) of the TP uplift; 4) abrupt climatic changes; and 5) comparisons between the results of numerical simulations and geological evidences.