Drug development is, in essence, the answering of scientific questions related to the effects of the intended new medicine. This process starts with preclinical research and proceeds with clinical testing. Especially for innovative drugs, this proceeds along a number of cycles in which the questions are answered by learning from informative studies and subsequent confirmation in more pragmatic studies. Many first-in-human studies and other human pharmacology studies are not designed to be informative but use standard designs and answer generic questions about tolerability and safety. Despite several recent and eloquent pleas for more integrated and quantitative drug development, signs of a strong uptake of this are lacking. In this article, an orderly method for the determination of objective human pharmacology studies is given. The objectives of the study and the expected pharmacology and pharmacokinetics of the compound determine the optimal design; and several general design models and guidelines are given for the design of informative human pharmacology studies.