Simple SummaryRepeat breeder cow (RBC) syndrome encompasses cows failing three or more times to become pregnant, but with the special characteristic that their estrous cycles have a normal duration. Farmers and technicians commonly feel incapable of addressing this reproductive issue, and after numerous unsuccessful attempts to conceive, it is often necessary to cull cows. Important economic losses are linked to RBC syndrome due to diagnosis, therapy, or reduced milk production, among others. This review compiles information about recent knowledge on the pathogenesis of RBC syndrome, describes treatments that could be efficient, analyzes the risk factors involved, and slightly evaluates their economic impact on farms. While it is difficult to resolve certain cases due to the multicausal nature of this syndrome, remedial therapy and management strategies are listed.AbstractCows can have difficulties becoming pregnant, and in certain cases, these reproductive failures do not have an evident cause. Furthermore, when these failures are repeated three or more times with estrous cycles of normal duration and in the absence of evident clinical signs, it is considered repeat breeder cow (RBC) syndrome. A substantive incidence of RBC syndrome has been reported all over the world, which severely affects the farm economy. This paper reviews those studies particularly focused on RBC syndrome from 2000 to 2023 but also includes consolidated information until this date. Hormonal imbalances, undetectable oviductal or uterine defects, or poor oocyte or embryo quality have been reported as causes of RBC syndrome, while subclinical endometritis has been considered a relevant causal agent. However, it is unresolved why this condition is recurrent in certain animals, despite the implementation of corrective management actions or treatments. Recent studies evaluate the putative role of certain genes, factors, hormones, or proteins in the pathogenesis of RBC syndrome. Numerous risk factors contribute to the appearance of this syndrome, and some of them could be mitigated to partially prevent this infertility, while others cannot be changed. Due to the complexity of this syndrome, it is important to increase knowledge about the mechanisms involved, develop new diagnostic tools to differentiate causal agents, and implement new treatments to restore fertility. There is consensus about the huge repercussions of this syndrome on farm profitability, but further studies are now needed to describe its economic impact.