In the eukaryotic cell an intrinsic mechanism is present providing the ability to defend itself against external stressors from various sources. This defense mechanism probably evolved from the presence of a group of chaperones, playing a crucial role in governing proper protein assembly, folding, and transport. Upregulation of the synthesis of a number of these proteins upon environmental stress establishes a unique defense system to maintain cellular protein homeostasis and to ensure survival of the cell. In the cardiovascular system this enhanced protein synthesis leads to a transient but powerful increase in tolerance to such endangering situations as ischemia, hypoxia, oxidative injury, and endotoxemia. These so-called heat shock proteins interfere with several physiological processes within several cell organelles and, for proper functioning, are translocated to different compartments following stress-induced synthesis. In this review we describe the physiological role of heat shock proteins and discuss their protective potential against various stress agents in the cardiovascular system.