Cells are exposed to various intrinsic and extrinsic stresses in both physiological and pathological conditions. To adapt to those conditions, cells have evolved various mechanisms to cope with the disturbances in protein demand, largely through the Unfolded Protein Response (UPR) in the Endoplasmic Reticulum (ER), but also through the Integrated Stress Response (ISR). Both responses initiate downstream signaling to transcription factors that, in turn, trigger adaptive programs and/or in the case of prolonged stress, cell death mechanisms. Recently, non-coding RNAs, including microRNA and long non-coding RNA, have emerged as key players in the stress responses. These non-coding RNAs act as both regulators and effectors of the UPR, and fine-tune the output of the stress signaling pathways. Although much is known about the UPR and the cross-talk that exists between pathways, the contribution of small non-coding RNA has not been fully assessed. Herein we bring together and review the current known functions of non-coding RNA in regulating adaptive pathways in both physiological and pathophysiological conditions, illustrating how they operate within the known UPR functions and contribute to diverse cellular outcomes.