Recently, significant advances in our understanding of embryo implantation have been made using animal models, notably in the mouse and nonhuman primates. However, the determination of the molecular and cellular events that underpin the early stages of implantation in the human remains an intractable problem, in part due to the inaccessibility of early human implantation sites. In the absence of in vivo implantation sites, several experimental in vitro model systems have been developed recently that mimic the different stages of human embryo implantation that occur in vivo during the first few weeks of pregnancy. These include solid-phase assays of blastocyst attachment and trophoblast invasion, and two- and three-dimensional blastocyst-endometrial cell cocultures. An important feature of such models is that they allow functional studies to be performed and are not restricted to generating descriptive data. These models have the potential to make an important contribution to the development of new therapeutic and diagnostic strategies for implantation failure in the future, as well as toxicity testing. We describe the strengths and weakness of the models and some of the advances that have been made by the use of these in vitro models.