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‘There are more things between heaven and earth…’ Despite the progress of science during the past four centuries, Shakespeare''s words did not lose their actuality. Knowledge about the etiology of diseases is still limited, and for many life-threatening illnesses no effective treatments exist. Nature always has been a valuable source of drugs and, despite the unprecedented opportunities afforded by medicinal chemistry, continues to deliver lead compounds. Traditionally, research on natural sources was focused on terrestrial plants and microorganisms. More recently, however, organisms of marine origin are also being investigated. Here, the possibilities of unconventional and hardly explored sources are discussed. [Copyright &y& Elsevier]

Prospecting the full biodiversity of nature to find leads for new drugs is not necessary. Because finding leads is aimed at identifying biological activity, structure is of secondary importance. Furthermore, although natural chemical diversity might be unrivalled, functional diversity is bound to be considerably less. It is likely that many millions of chemically distinct molecules exist in nature but it is inconceivable that the number of different biological functions is near this number. This is corroborated by knowledge obtained from the genome sequences of an increasing number of species. It is unlikely that ligands for specific molecular targets are restricted to one species and even individual compounds are often found in more than one species. Important molecular mechanisms are likely to be ubiquitous and there are no a priori reasons to assume that some are restricted to, for example, tropical rainforests. Thus, there are no obvious advantages of ‘biodiversity prospecting’, which will, possibly, endanger fragile ecosystems in the search for rare species. [Copyright &y& Elsevier]