Living organs use oxygen to create energy; however, they are surrounded by risks to be damaged by reactive oxygen species (ROS) generated during various metabolic process. To protect from ROS-mediated damage, organs have acquired defense systems. Of the defense systems, inductive responses of stress proteins including heme oxygenase (HO) and metallothionein (MT) have currently been received great attention. HO is the rate-limiting enzyme of heme degradation and only HO-1 is an inducible isozyme among three isozymes under various oxidative stimuli. MT is rather a small, cystein-rich, metal-binding protein and MT-1 and -2 response to oxidative stress. HO-1 and MT induction have been shown to confer protection against oxidative stress. Both HO-1 and MT (MT-1 & -2) gene expressions are greatly induced by similar oxidative stimuli. However, signal transduction pathways seem to be different with each gene. In this mini-review, recent studies examined oxidative stress-mediated induction of HO-1 and MT, including some of human diseases, are introduced and its molecular mechanisms are compared. Functional roles of HO-1 and MT inductions playing in some of human diseases are also introduced and discussed.