Many biological studies, drug screening methods, and cellular therapies require culture and manipulation of living cells outside of their natural environment in the body. The gap between the cellular microenvironment in vivo and in vitro, however, poses challenges for obtaining physiologically relevant responses from cells used in basic biological studies or drug screens and for drawing out the maximum functional potential from cells used therapeutically. One of the reasons for this gap is because the fluidic environment of mammalian cells in vivo is microscale and dynamic whereas typical in vitro cultures are macroscopic and static. This presentation will give an overview of efforts in our laboratory to develop microfluidic systems that enable control of both the chemical and fluid mechanical environment of cells. The technologies and methods close the physiology gap to provide biological information otherwise unobtainable and to enhance cellular performance in therapeutic applications. A key technological need is to integrate sensors to refine device design and operating parameters as well as to monitor real time cellular responses. Specific biomedical topics that will be discussed include, microfluidic models of small airway injuries with pressure sensing and microfluidic liver/cancer cell culture with oxygen sensing. Additionally, microfluidic circuitry with hardware embedded flow control systems that automatically perform sophisticated fluid manipulations powered only by hand squeezing of the device will be presented. This type of capability may be useful for point-of-care diagnostic devices in resource poor environments.