Unfolding or misfolding of proteins constitutes a fundamental threat to all living cells. In eukaryotes, proteins can be unfolded or misfolded in a variety of subcellular compartments such as cytoplasm, mitochondria, and peroxisomes, but the risk of protein misfolding is particularly acute in the endoplasmic reticulum (ER), in which newly synthesized secretory and transmembrane proteins attain their proper tertiary structure. Efficient quality control systems have evolved to prevent incompletely folded molecules from moving along the secretory pathway. Accumulation of misfolded proteins in the ER would detrimentally affect the function and/or localization of the approximately one-third of all cellular proteins that translocate into the ER after synthesis on membrane-bound ribosomes. Eukaryotic cells have three different mechanisms for dealing with an accumulation of unfolded proteins in the ER: transcriptional induction, translational attenuation, and degradation (Figure 1). This minireview focuses on new pieces of the puzzle that are important for understanding the molecular mechanisms of the induction and attenuation systems, most of which were discovered in the space of only one year after publication of a comprehensive review of this field (