A trillion different microbial species have been evolving for some 3.5 billion years, producing ever more complex active secondary metabolites. The sea is a cauldron of a great diversity of useful and valuable compounds. This Special Issue focused on studies of marine microbe natural products for discovering compounds useful to humankind. Papers were collected that provide up-to-date information regarding the characterization of marine microbes' metabolic diversity and the evaluation of the therapeutic potential of marine microbes' metabolites. Most of the articles in this book deal with marine fungi, biological and chemical diversity, and their active metabolites. This may be a sign that marine fungi have been under studied to date and are perceived by many researchers as an important source of discovery in this field. A best practices guide for the isolation of marine fungi from different matrixes and their conservation is also presented. The comparison of the phylogenetic and metabolomic profiles of microalgae from different lineages provides novel insights into the potential of chemotaxonomy in marine phytoplankton, showing a good overlap of phylogenetic and chemotaxonomic signals.