We are learning much about how structure forms, in particular how clusters as nodes in the cosmic web evolve and accrete matter, and about the physical processes within these objects. In the next decade, the study of clusters will enable us to tackle important questions regarding the nature of Dark Matter and Dark Energy, how clusters co-evolve with super-massive black holes at their centers, and to advance our knowledge about fundamental plasma astrophysics. This science white paper outlines the key questions and research opportunities in cluster astrophysics that are emerging in the coming decade and beyond, and serves as an overview to other cluster related white papers.