The ability of anaerobic microorganisms to proliferate under extreme conditions is of widespread importance for microbial physiology, remediation, industry, and evolution. The halophilic alkalithermophiles are a novel group of polyextremophiles. Tolerance to alkaline pH, elevated NaCl concentrations, and high temperatures necessitates mechanisms for cytoplasmic pH acidification; permeability control of the cell membrane; and stability of proteins, the cell wall, and other cellular constituents to multiple extreme conditions. Although it is generally assumed that extremophiles growing at more than one extreme combine adaptive mechanisms for each individual extreme, adaptations for individual extremes often counteract each other. However, in alkaline, hypersaline niches heated via intense solar irradiation, culture-independent analyses have revealed the presence of an extensive diversity of aerobic and anaerobic microorganisms belonging to Bacteria and Archaea that survive and grow under multiple harsh conditions. Thus, polyextremophiles must have developed novel adaptive strategies enabling them to grow and proliferate under multiple extreme conditions. The recent isolation of two novel anaerobic, halophilic alkalithermophiles, Natranaerobius thermophilus and Halonatronum saccharophilum, will provide a platform for detailed biochemical, genomic, and proteomic experiments, allowing a greater understanding of the novel adaptive mechanisms undoubtedly employed by polyextremophiles. In this review, we highlight growth characteristics, ecology, and phylogeny of the anaerobic halophilic alkalithermophiles isolated. We also describe the bioenergetic and physiological problems posed by growth at the multiple extreme conditions of alkaline pH, high NaCl concentration, and elevated temperature under anoxic conditions and highlight recent findings and unresolved problems regarding adaptation to multiple extreme conditions.