Apoptosis is often deregulated in a number of human diseases. Heat-induced apoptosis is a model system for studying the consequences of protein misfolding and is mediated by the Bcl-2 family of proteins. This family consists of both pro-apoptotic and anti-apoptotic members that control mitochondrial integrity. The BH3-only pro-apoptotic members are strong inducers of apoptotic cell death. Protein damaging stress can activate a process of cellular destruction known as apoptosis. The pro-apoptotic BH3-only proteins and transcription factors activate this death pathway by inhibiting the anti-apoptotic Bcl-2 family proteins eliminating cancer cells in a short period of time.