This white paper, submitted for the Plasma 2020 Decadal Survey, concerns the physics of weakly collisional, high-beta plasmas -- plasmas in which the thermal pressure dominates over the magnetic pressure and in which the inter-particle collision time is comparable to the characteristic timescales of bulk motions. This state of matter, although widespread in the Universe, remains poorly understood: we lack a predictive theory for how it responds to perturbations, how it transports momentum and energy, and how it generates and amplifies magnetic fields. Such topics are foundational to the scientific study of plasmas, and are of intrinsic interest to those who regard plasma physics as a fundamental physics discipline. But these topics are also of extrinsic interest: addressing them directly informs upon our understanding of a wide variety of space and astrophysical systems, including accretion flows around supermassive black holes, the intracluster medium (ICM) between galaxies in clusters, and regions of the near-Earth solar wind. Specific recommendations to advance this field of study are discussed.