History shows that metal-based drugs and remedies have been known and used since very ancient times. For example, silver was employed in the treatment of wounds and ulcers according to the Greek physician Hippocrates, but its antimicrobial properties had probably been recognized long before because it was used to make vessels for storing liquids in pure form. The ancient Egyptians also knew how to sterilize water with copper. The medical use of gold can be dated back to 2500 B.C. in China. However, the new era of metal-based medicine started almost 50 years ago when cisplatin was shown to inhibit cellular division in E. coli, thereby leading to the first studies of its antitumor activity in rats and its assessment as one of the most powerful drugs for use against different types of cancer, although many other novel metal-based drugs are promising and they are attracting growing attention in modern clinical medicine. Gold salts and arsenic compounds have been in use for decades in the treatment of rheumatoid arthritis and syphilis, respectively, but studies of cisplatin have definitely shifted the attention of researchers to the pool of transition “heavy” metals as potential therapeutic agents. Rhodium, iridium, palladium, osmium, and the other so-called noble elements have been the subjects of intensive investigations, thereby leading to the production of a series of complex compounds with remarkable anticancer activities, as well as antirheumatic, antimalarial, and antimicrobial drugs. The number of published studies in this field is huge and they have already been the subjects of careful review. In this review, we provide a detailed account of the latest results (2010–2013) and their potential uses in the cure of severe diseases.