Phosphorus-based ligands are an extremely important class of ligand and they have found many applications, especially in homogeneous catalysis. In addition, a phosphine ligand is found in a gold drug used to treat rheumatoid arthritis. Since metal compounds are also widely used to treat cancer many studies on the anticancer activity of metal–phosphine complexes have been conducted. In this chapter we describe recent highlights in the field, centered on platinum, ruthenium and gold complexes. From this overview it is clear that phosphorus-based ligands offer a number of important advantages compared to other types of ligands. It also becomes clear that studies are in a comparatively early stage and that more attention should be directed towards the design and synthesis of phosphine and other phosphorus ligands for medicinal applications in metal-based chemotherapeutics. Examples of metal–phosphine compounds that target critical enzymes in cancer indicates that these compounds operate via mechanisms quite distinct from other metal-based drugs which damage DNA, and consequently, facilitates rational drug design.