The article reviews the in vivo aspects of protein folding and quality control, highlighting the importance of molecular chaperones in maintaining proteostasis. It discusses how newly synthesized proteins are at risk of misfolding and forming toxic aggregates in the crowded cellular environment. The role of molecular chaperones, such as chaperonins (Hsp60), Hsp70, and Hsp90, in guiding nascent proteins along productive folding pathways is emphasized. The article also explores the mechanisms of these chaperones, including their interaction with the ribosome and their ability to prevent aggregation. The authors explain how the proteostasis network (PN) integrates chaperones, the ubiquitin-proteasome system, and autophagy to maintain protein homeostasis. They highlight the decline of PN capacity during aging, which facilitates neurodegeneration and other chronic diseases associated with protein aggregation. The review concludes by discussing the potential of targeting the PN for pharmacological intervention in these pathologies.The article reviews the in vivo aspects of protein folding and quality control, highlighting the importance of molecular chaperones in maintaining proteostasis. It discusses how newly synthesized proteins are at risk of misfolding and forming toxic aggregates in the crowded cellular environment. The role of molecular chaperones, such as chaperonins (Hsp60), Hsp70, and Hsp90, in guiding nascent proteins along productive folding pathways is emphasized. The article also explores the mechanisms of these chaperones, including their interaction with the ribosome and their ability to prevent aggregation. The authors explain how the proteostasis network (PN) integrates chaperones, the ubiquitin-proteasome system, and autophagy to maintain protein homeostasis. They highlight the decline of PN capacity during aging, which facilitates neurodegeneration and other chronic diseases associated with protein aggregation. The review concludes by discussing the potential of targeting the PN for pharmacological intervention in these pathologies.