Display omitted The biological activity and structural diversity of natural products are unsurpassed by any available synthetic screening libraries. As such, these privileged scaffolds serve as important, biologically prevalidated platforms for the design of compound libraries in the search for new drug candidates. Recent progress has focussed on improving the potency, selectivity and pharmacokinetics of bioactive natural products through structural modification, leading to the emergence of a number of drug-like lead compounds. Here, we review recent advances in the exploitation of terpenoid, polyketide, phenylpropanoid and alkaloid natural product scaffolds for inspiration in the design and development of important new drug candidates.