Weather fluctuation triggers a suite of abiotic stress factors to induce the production of reactive oxygen species (ROS). The phenomenon has worldwide relevance to food availability and food security, as well as plant development, growth, and survival. Under weather fluctuation, osmolytes are produced in response by plants to act as compatible solutes. Besides inducing homeostasis, osmolytes increase the water potential of the plant, adjust intracellular osmotic pressure to keep cell turgidity in check, and adjust redox metabolism to trap reactive oxygen species (ROS) excess to regulate oxidative as well as osmotic stress imposed on cellular processes. Carbohydrates, proline, glycine-betaine, and polyamines form a leading group of osmolytes. The main role of these osmolytes is to stabilize intracellular as well as external osmotic gradients. Furthermore, they reverse oxidative damage caused by other reactive oxygen species (ROS) on plant cellular machinery, i.e., hydroxyl ions, superoxide ions, and hydrogen peroxide. Plant developmental regulators such as abscisic acid, brassinosteroids, cytokinins, ethylene, jasmonates, and salicylic acid regulate osmolyte production. It is therefore of essential interest to analyze the manner by which plants subjected to abiotic stress use phytohormones to regulate the production of osmolytes. This chapter explores the molecular processes and possible roles of osmolytes, such as their connection to plants’ resilience to abiotic stress, the dynamics of their behavior in reaction to changes in their environment, and the resolution of signal transduction pathways. Furthermore, transgenic plants expressing genes for certain osmolytes demonstrated enhanced resilience to various forms of abiotic stresses.