The discovery of novel anticoagulants, and the search for novel orally active agents in particular, has been a long and difficult journey. However, the recent (2008) launches of Bayer’s Factor Xa inhibitor (Rivaroxaban, BAY 59-7939) and Boehringer Ingelheim’s Thrombin inhibitor (Dabigatran, Pradaxa/Pradax, BIBR 953) are the first fruits of those efforts and both have the potential to offer marked improvements over the current clinical standards of care. Whilst the discovery of both of these compounds has already been extensively reported (e.g. see leading J.Med.Chem articles for Dabigatran and Rivaroxaban respectively) and are well known stories in the medicinal chemistry community, the latest edition of Nature Reviews|Drug Discovery carries a really nice case history, from Bayer scientists, outlining the discovery of Rivaroxaban. The review provides an excellent, concise overview of the anticoagulant field; the history behind the search for novel oral agents; the validation of factor Xa as a target; the discovery of rivaroxaban (including a brief overview of the key SAR and the somewhat serendipitous discovery of the important non-basic, chloro-thiophene binding motif); the clinical development of rivaroxaban; and an update on the current state-of-play and outlook for the future in the area. A really good read, particularly for those less familiar with the area or looking for a brief update on the more recent clinical studies.