'Clean' or 'dirty' - Just how selective do drugs need to be?

Chemotherapy has developed largely on the basis of searching for chemicals with selective toxicity, targeting a specific step or receptor in a disease process without negatively impacting on normal physiology. The desire for 'clean' drugs that act on a single target and thus avoid side effects has led to ever-increasing timeframes for introducing new drugs to humans. This has led to reappraisal of how selective drugs need to be. Examples here of compounds from common drug classes (kinase inhibitors, protease inhibitors, G protein coupled receptors ligands, non-steroidal anti-inflammatory drugs, statins, antibodies) highlight current debate on the merits of target selectivity versus target promiscuity in the development of drugs for inflammation, cancer, cardiovascular, central nervous system and infectious diseases.