The discovery and exploitation of new drug targets is a key focus for both the pharmaceutical industry and academic biomedical research. To provide an insight into trends in the exploitation of new drug targets, we have analysed the drugs that were approved by the US Food and Drug Administration during the past three decades and examined the interactions of these drugs with therapeutic targets that are encoded by the human genome, using the DrugBank database and extensive manual curation. We have identified 435 effect-mediating drug targets in the human genome, which are modulated by 989 unique drugs, through 2,242 drug–target interactions. We also analyse trends in the introduction of drugs that modulate previously unexploited targets, and discuss the network pharmacology of the drugs in our data set.