Metalloproteins play critical roles in living cells. There are more than a dozen metals with known or suspected biological functions, which include determining structure, electron transfer, and catalysis. The binding of a metal cofactor can generate beautifully colored proteins, but, more importantly, these metalloproteins function in essentially every metabolic pathway, greatly extending the chemistry past those that are available to a living cell with only the side groups of the 20 amino acids. The number and types of metalloproteins in cells remain surprisingly underappreciated, and only recently, with the advent of coupled purification and detection techniques, such as capillary electrophoresis and inductively coupled plasma emission mass spectrometry, is the true extent of the metalloproteome being revealed. Proteins from hyperthermophilic microorganisms are of particular utility for studying metalloproteins due to their extreme stability and relative ease of purification, both from native and recombinant sources. Herein we focus on the metalloproteins that have been characterized from some model hyperthermophilic systems with an emphasis on their properties and the roles that they play in primary metabolism.