Fanconi anemia is a genetically heterogeneous disorder associated with 
chromosome instability and a highly elevated risk for developing cancer. The 
mutated genes encode proteins involved in the cellular response to DNA 
replication stress. Fanconi anemia proteins are extensively connected with DNA 
caretaker proteins, and appear to function as a hub for the coordination of DNA 
repair with DNA replication and cell cycle progression. At a molecular level, 
however, the raison d'être of Fanconi anemia proteins still remains largely 
elusive. The thirteen Fanconi anemia proteins identified to date have not been 
embraced into a single and defined biological process. To help put the Fanconi 
anemia puzzle into perspective, we begin this review with a summary of the 
strategies employed by prokaryotes and eukaryotes to tolerate obstacles to the 
progression of replication forks. We then summarize what we know about Fanconi 
anemia with an emphasis on biochemical aspects, and discuss how the Fanconi 
anemia network, a late acquisition in evolution, may function to permit the 
faithful and complete duplication of our very large vertebrate chromosomes.