With heightened concerns on carbon dioxide (CO2) emissions from coal power plants, there has been a major emphasis in recent years on development of safe and economical geological carbon sequestration (GCS) technology. However, the detailed multiphase fluid dynamics and processes of GCS are not fully understood because various CO2 trapping mechanisms in geological formations have large variations in both spatial and temporal scales. As a result, there remain many uncertainties in determining the sequestration capacity of the reservoir and the safety of sequestered CO2 due to leakage. Furthermore, the sequestration efficiency is highly dependent on the CO2 injection strategy, which includes injection rate, injection pressure, and type of injection well, and its orientation, etc. The goal of GCS is to maximize the sequestration capacity and minimize the plume migration by optimizing the GCS operation. In this paper, first the basic fluid dynamics and trapping mechanisms for CO2 sequestration are briefly discussed. They are followed by a brief summary of current GCS projects worldwide with special emphasis on those in the United States. Majority of the paper is devoted to the numerical modeling, simulation, and optimization of CO2 sequestration in saline aquifers at macro spatial scales of a few to hundreds of kilometers and macro temporal scales of a few to hundreds of years. Examples of numerical simulations of a few large industrial scale projects are presented. The optimization studies include the investigation of various injection and well placement strategies to determine the optimal approach for maximizing the storage and minimizing the plume migration.