 Study of extremophiles is one of the most exciting areas of research in recent decades. Despite the latest advances we are just in the beginning of exploring and characterizing the world of extreme organisms. This special issue discusses several aspects of these fascinating organisms, exploring their habitats, biodiversity, ecology, evolution, genetics, biochemistry, and biotechnological applications in a collection of exciting reviews and original articles. This article was authored by Pabulo Enrique Rampolado.