Enzymatic hydrolysis with continuous removal of soluble compounds can increase hydrolysis rates and increase the usable life of expensive enzymes. Following hydrolysis, process simulations show that water can be more efficiently removed via sugars concentration prior to fermentation rather than via distillation afterwards. Evaporation is also effective at removing volatile inhibitors and nanofiltration can be tailored to remove more than 50% of inhibitors while concentrating sugars. However, both processes suffer from fouling and can lead to concentration of some of the inhibitors, requiring an inhibitor removal step. Polyethylenimine flocculation and resin wafer electrodeionization have been demonstrated as effective processes, removing over 68% of aldehydes and greater than 70% of acetic acid and other ionic species. After concentrating sugars and removing sufficient inhibitory compounds, continuous fermentation with microfiltration cell recycle has been shown to improve volumetric ethanol productivity by 5 to 10 times and reduce inhibition. Challenges related to high gravity, high cell density systems and microfiltration fouling, along with mitigating solutions will be discussed.