The process of discovering new drugs and getting regulatory approval is becoming ever more costly. At present, the total turnover of the world's pharmaceutical industry is roughly $350–$400 billion, while the cost of R&D is estimated at about $45 billion per year. In comparison, R&D investment was $5 billion in 1986 and $30 billion in 2001. In spite of the significantly larger spending on R&D, the total number of new chemical entities (NCEs) approved by the US Food and Drug Administration has not shown a commensurate increase. The number of NCEs licensed in a given year has remained relatively constant over the years, varying from 20 in 1986 to between 25 and 30 during 1999–2001. Simple arithmetic therefore suggests that the cost of discovering a new drug, defined as the ratio of the total R&D expenditure per year divided by the number of NCEs licensed in that year, has climbed from about $250 million in 1986 to nearly $1 billion today. Of this amount, roughly half, or $400–$500 million, represents the actual expenditure, while the remainder represents the opportunity cost; that is, the cost of locking up one's capital over a long period.