The use of metals in medicine has grown impressively in recent years as a result of greatly advanced understanding of biologically active metal complexes and metal-containing proteins. One landmark in this area was the introduction of cisplatin and related derivatives as anticancer drugs. As the body of literature continues to expand, it is necessary to inspect sub-classes of this group with more acute detail. This chapter will review preclinical research of cobalt complexes coordinated by Schiff base ligands. Cobalt-Schiff base complexes have a wide variety of potential therapeutic functions, including as antimicrobials, anticancer agents, and inhibitors of protein aggregation. While providing a broad introduction to this class of agents, this chapter will pay particular attention to agents for which mechanisms of actions have been studied. Appropriate methods to assess activity of these complexes will be reviewed, and promising preclinical complexes in each of the following therapeutic areas will be highlighted: antimicrobial, antiviral, cancer therapy, and Alzheimer's disease.