Members of the genus Dunaliella are exceptional among marine algae, and photosynthetic eukaryotes in general, in their ability to adapt to broadly varying environmental conditions, ranging from the mild to the extreme. This chapter describes mechanisms underlying the extraordinary adaptive capabilities of D. bardawil and D. salina to excessive light fluxes or multimolar salinities as revealed in differential scans for genes/proteins specifically upregulated/accumulated in cells challenged with these stresses. The responses to light stress include the accumulation of Cbr, a protein identified in LHCII protein-pigment complexes enriched in zeaxanthin and lutein and assigned a role in a photoprotective mechanism operating independently of a trans-thylakoid pH gradient. Related mechanisms have now been described also in higher plants. The salt-induced responses included the induction of fatty acid elongase and corresponding modifications of fatty acid composition of microsomal membranes, a unique transferrin protein involved in iron uptake and two salt-inducible plasma membrane α-type carbonic anhydrases (dCA I and dCA II) implicated in alleviating salt-imposed limitations on CO2 availability. The Dunaliella carbonic anhydrases differ drastically from animal and Chlamydomonas reinhardtii counterparts, that are sensitive to inhibition by halide and other anions, in retaining activity in zero to at least 3.0 M NaCl. The striking functional singularity of the Dunaliella carbonic anhydrases drew our attention to a largely neglected aspect of the salt-adaptability of Dunaliella, i.e., the role played by protein molecular adaptation. Critical insights into the structural basis of the exceptional anion resistance/salt tolerance of dCAs were gained from the crystal structure determined for dCA I and dCA II (the first structures determined for Dunaliella proteins), that differed from all previously-determined CA structures in exhibiting a negative surface electrostatic 328potential, intermediate between typical potentials of salt-sensitive and halophilic proteins. The significance of these electrostatic features in dCAs halotolerance were supported by the prediction and biochemical confirmation of the unanticipated halotolerance of a mammalian CA, the murine CA XIV.