Missing information about reproductive processes is an important barrier to conception and live birth among infertile couples. In vitro and genetic techniques have been informative, but not enough is known about potential defects in fertilization, implantation and early embryo development to define explicit infertility diagnoses and direct specific treatment. Study of gamete quality is needed because endocrine and ultrasound measurements in the female cannot determine oocyte quality and semen analysis in the male is a limited predictor of fertilizing ability. Also, more study would help in understanding the conditions in the Fallopian tube and elsewhere that foster fertilization and embryo development. Research in related subjects is also needed: after many years of enquiry, there exists little or no evidence to determine how and if endometriosis causes subfertility. In contrast, the recently described impact of smoking in males is large, clinically important and possibly reversible. Missing information limits the choice of specific treatment, puts a ceiling on the overall prognosis, increases the likelihood of persistent infertility and forms a barrier to understanding the broader meanings of success in the management of infertility.