Amoebozoans are in many aspects interesting research objects, as they combine features of single-cell organisms with complex signaling and defense systems, comparable to multicellular organisms. 'Acanthamoeba castellanii' is a cosmopolitan species and developed diverged feeding abilities and strong anti-bacterial resistance; 'Entamoeba histolytica' is a parasitic amoeba, who underwent massive gene loss and its genome is almost twice smaller than that of 'A. castellanii'. Nevertheless, both species prosper, demonstrating fitness to their specific environments. Here we compare transcriptomes of 'A. castellanii' and 'E. histolytica' with application of orthologs' search and gene ontology to learn how different life strategies influence genome evolution and restructuring of physiology. 'A. castellanii' demonstrates great metabolic activity and plasticity, while 'E. histolytica' reveals several interesting features in its translational machinery, cytoskeleton, antioxidant protection, and nutritional behavior. In addition, we suggest new features in 'E. histolytica' physiology that may explain its successful colonization of human colon and may facilitate medical research.