Life in high salinity environments poses challenges to cells in a variety of ways: maintenance of ion homeostasis and nutrient acquisition, often while concomitantly enduring saturating irradiances. Dunaliella salina has an exceptional ability to thrive even in saturated brine solutions. This ability has made it a model organism for studying responses to abiotic stress factors. Here we describe the occurrence of unique gene families, expansion of gene families, or gene losses that might be linked to osmoadaptive strategies. We discovered multiple unique genes coding for several of the homologous superfamily of the Ser-Thr-rich glycosyl-phosphatidyl-inositolanchored membrane family and of the glycolipid 2-alpha-mannosyltransferase family, suggesting that such components on the cell surface are essential to life in high salt. Gene expansion was found in families that participate in sensing of abiotic stress and signal transduction in plants.One example is the patched family of the Sonic Hedgehog receptor proteins, supporting a previous hypothesis that plasma membrane sterols are important for sensing changes in salinities in D. salina. We also investigated genome-based capabilities regarding glycerol metabolism and present an extensive map for core carbon metabolism. We postulate that a second broader glycerol cycle exists that also connects to photorespiration, thus extending the previously described glycerol cycle. Further genome-based analysis of isoprenoid and carotenoid metabolism revealed duplications of genes for 1-deoxy-D-xylulose-5-phosphate synthase (DXS) and phytoene synthase (PSY), with the second gene copy of each enzyme being clustered together. Moreover, we identified two genes predicted to code for a prokaryotic-type phytoene desaturase (CRTI), indicating that D. salina may have eukaryotic and prokaryotic elements comprising its carotenoid biosynthesis pathways. In brief, our genomic data provide the basis for further gene discoveries regarding sensing abiotic stress, the metabolism of this halophilic alga, and its potential in biotechnological applications.