Accumulation of intracellular damage is an almost universal hallmark of aging. An improved understanding of the systems that contribute to cellular protein quality control has shed light on the reasons for the increased vulnerability of the proteome to stress in aging cells. Maintenance of protein homeostasis, or proteostasis, is attained through precisely coordinated systems that rapidly correct unwanted proteomic changes. Here we focus on recent developments that highlight the multidimensional nature of the proteostasis networks, which allow for coordinated protein homeostasis intracellularly, in between cells and even across organs, as well as on how they affect common age-associated diseases when they malfunction in aging.